Publications by authors named "Satoshi Ikeda"

299 Publications

Identification and Characteristics of Co-isolation of Multiple Nontuberculous Mycobacteria.

Intern Med 2021 Apr 26. Epub 2021 Apr 26.

Division of Pulmonary Medicine, Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan.

Objective Although multiple non-tuberculous mycobacteria (NTM) species can be isolated from the same patient, little has been reported on co-isolation. We clarified the trends and characteristics of the co-isolation of multiple NTM species. Methods To collect data on multiple NTM isolation, we first extracted all patients who visited our hospital from 2006 through 2015 with a diagnosis of NTM lung diseases other than Mycobacterium avium complex (MAC) and then reviewed their medical records to evaluate the co-isolation of multiple NTM species. Results Of 213 patients with non-MAC lung disease, the most common NTM species was M. gordonae (32%), followed by M. kansasii (20%) and M. abscessus (14%). Non-MAC NTM lung disease tended to be associated with middle age with a low body mass index and male predominance. Multiple NTM species were isolated from 55 (26%) of the 213 patients. The clinical characteristics associated with multiple NTM species isolation included female predominance, never smokers and the absence of cavity lesions in the lungs. The highest co-isolation rate was observed in patients with M. gordonae isolation (30%), followed by M. furtuitum isolation (26%) and M. abscessus isolation (20%). Only MAC was isolated when co-isolated with M. abscessus. Among M. szulgai, M. peregrinum and M. terrae isolation, no other NTM species were detected. Conclusion Co-isolation of multiple NTM species was not uncommon, with 26% of patients with non-MAC NTM lung diseases showing co-isolation with multiple NTM species. Each NTM species had distinct characteristics in terms of co-isolation.
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http://dx.doi.org/10.2169/internalmedicine.5300-20DOI Listing
April 2021

Association between the Wechsler Adult Intelligence Scale III and early return to work after traumatic brain injury.

Work 2021 ;68(4):1101-1111

Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo City, Hokkaido, Japan.

Background: Residual capacity evaluation via neuropsychological testing can facilitate the development of a rehabilitation plan in patients following a traumatic brain injury (TBI).

Objective: This study aimed to confirm the tasks that patients must perform well for early return to work (RTW) following TBI using the Wechsler Adult Intelligence Scale III (WAIS-III).

Methods: In total, 40 male and 13 female patients who suffered from neurobehavioral disabilities following TBI were recruited and classified into two groups: the successfully returned to work group (SRTW-G; n = 22) and the unsuccessfully returned to work group (USRTW-G; n = 31). The outcomes assessed by WAIS-III and the time to RTW were compared between the SRTW-G and USRTW-G groups. Multiple logistic regression, multiple regression analysis, and Cox regression were employed to assess differences between the groups.

Results: The Comprehension and Letter-Number Sequencing subtests of the WAIS-III were significantly correlated with early RTW more than the other subtests.

Conclusions: We found that, as reflected in the two subtests, patients with TBI must be able to perform well in the following tasks for early RTW: Retention of information for short time periods, information processing, and social judgment based on the knowledge of the patient's experience.
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http://dx.doi.org/10.3233/WOR-213440DOI Listing
January 2021

Clinical characteristics of Japanese patients with moderate to severe COVID-19.

J Infect Chemother 2021 Jun 4;27(6):895-901. Epub 2021 Mar 4.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan. Electronic address:

Introduction: Although several reports on the risk factors for severe disease of COVID-19 already exist, reports on effective early indicators are still limited, especially from Japan. This study was conducted to clarify the patient's characteristics whose disease progressed to severe status.

Methods: The medical records of all consecutive 300 Japanese patients hospitalized at our institution between February and November 2020 were retrospectively reviewed. The clinical characteristics were evaluated to compare between mild (no oxygen needed), moderate (oxygen needs of 1-4 L/min), and severe diseases (oxygen needs of 5 L/min or more).

Results: The median age was 68 years old, with 123 (41.0%) males and 177 (59.0%) females. Of these, 199 patients (66.3%), 55 patients (18.3%), 46 patients (15.3%) patients were in the mild disease, moderate disease, severe disease groups, respectively. Patients with severe disease were more likely to be older, have more comorbidities, and tended to have higher body mass index. In laboratory data, lymphocyte count, levels of C-reactive protein (CRP), LDH, and AST on admission were significantly associated with the severity. In multivariate analysis, age and CRP were the independent risk factors for severe disease (OR = 1.050, 1.130, respectively). The optimal cut-off value for age was 74 years old and that for CRP was 3.15 mg/dL.

Conclusions: Age and CRP were independently associated with disease severity of COVID-19 in multivariate analysis. Additionally, the numbers of underlying disease, lymphocyte count, and inflammatory markers such as LDH and D-dimer may also be related to disease severity.
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http://dx.doi.org/10.1016/j.jiac.2021.02.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931728PMC
June 2021

Effects of Vonoprazan on the Antiplatelet Function of Prasugrel Assessed by the VerifyNow P2Y Assay in Patients With Coronary Artery Disease.

Circ Rep 2020 Dec 18;3(1):26-33. Epub 2020 Dec 18.

Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan.

Vonoprazan is a potassium-competitive acid blocker increasingly used in Japan to prevent upper gastrointestinal bleeding in patients undergoing dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). Cytochrome P450 (CYP) 3A4 is involved in the primary metabolism of both vonoprazan and prasugrel. This raises concern about the possibility of a CYP3A4-mediated drug-drug interaction between vonoprazan and prasugrel that may lead to attenuation of prasugrel's antiplatelet effect. We evaluated 88 PCI patients who were taking either vonoprazan (n=45) or proton pump inhibitors (PPIs; n=43) in combination with DAPT (aspirin and prasugrel). Platelet reactivity on prasugrel was assessed using the VerifyNow P2Y assay. The primary endpoint was comparison of P2Y reaction units (PRU) between patients on vonoprazan and PPIs. PRU >208 and <85 were defined as high (HPR) and low (LPR) on-treatment platelet reactivity for prasugrel. PRU was comparable between patients receiving vonoprazan and PPIs (169±52 vs. 179±61, respectively; P=0.75). There were no significant differences between the vonoprazan and PPI groups in the prevalence of HPR (22% vs. 37%, respectively; P=0.16) and LPR (4 vs. 7%, respectively; P=0.48). The results were consistent regardless of the type of clinical presentation and DAPT duration. PRU under DAPT with aspirin plus prasugrel in patients receiving vonoprazan was not significantly different from that in patients receiving PPIs after PCI in routine clinical practice.
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http://dx.doi.org/10.1253/circrep.CR-20-0124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939790PMC
December 2020

Work-Family Spillover, Job Demand, Job Control, and Workplace Social Support Affect the Mental Health of Home-Visit Nursing Staff.

J UOEH 2021 ;43(1):51-60

Faculty of Medicine School of Nursing, Fukuoka University.

The primary purpose of this study was to clarify the path by which high job demands on home-visit nursing staff affect their mental health through work-family negative spillover (WFNS, FWNS). The secondary purpose was to clarify the path by which high job control and high social support in the workplace positively affect the mental health of nursing home-visit staff through work-family positive spillover (WFPS, FWPS). A cross-sectional survey using a self-administered questionnaire was conducted on 1,022 visiting nursing staff working at 108 visiting nursing stations in Fukuoka Prefecture in February, 2019. The measurement tools comprised sociodemographic factors, the Japanese version of the Survey Work-Home Interaction - NijmeGen (SWING-J), Job Content Questionnaire (JCQ-22), the Work-Family Culture Scale, and the K6 scale. Six models were determined in an analysis of the model: (1) working time load → WFNS → FWNS → psychological distress, (2) job demands → WFNS → FWNS → psychological distress, (3) job demands → psychological distress, (4) workplace support → job control → WFPS → psychological distress, (5) workplace support → WFPS → psychological distress, and (6) workplace support → psychological distress. This study clarified that job demands and working time load may adversely affect the mental health of home-visit nursing staff through the mediation of WFNS. It was also clarified that high job control and workplace support may have a positive effect on mental health through the mediation of WFPS.
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http://dx.doi.org/10.7888/juoeh.43.51DOI Listing
January 2021

Predictive factors for the long-term use of pirfenidone in patients with fibrosing interstitial lung disease.

Respir Investig 2021 Feb 19. Epub 2021 Feb 19.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan. Electronic address:

Background: Pirfenidone is an anti-fibrotic agent approved for idiopathic pulmonary fibrosis (IPF), and long-term treatment data and the effect of continuation after disease progression have been reported. The efficacy and safety of pirfenidone in fibrosing interstitial lung disease (ILD) patients without IPF have been recently reported in clinical trials; therefore, the benefits of long-term treatment are also expected. This study aims to analyze the long-term treatment data of pirfenidone and clarify the predictive factors for long-term use of pirfenidone in non-IPF patients.

Methods: We retrospectively reviewed the records of consecutive fibrosing ILD patients who started using pirfenidone between 2008 and 2014.

Results: Of the 266 fibrosing ILD patients, 167 patients had IPF, and 99 had non-IPF. Despite the non-significant differences in body size and pulmonary function between IPF and non-IPF patients, the non-IPF patients had better overall survival than the IPF patients (median 4.06 years vs. 2.09 years, p < 0.0001). In addition, the non-IPF patients had a significantly longer time to treatment discontinuation than the IPF patients (median 2.20 years vs. 1.20 years, p = 0.002). Multivariate logistic regression analysis for ≥2 years of use of pirfenidone showed that the percent predicted forced vital capacity (%FVC) and age were predictive factors common to both IPF and non-IPF patients.

Conclusions: Our results indicate that non-IPF patients can continue using pirfenidone for longer durations than IPF patients. Initiation of pirfenidone for fibrosing ILD patients with higher %FVC and younger age would lead to long-term use of pirfenidone.
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http://dx.doi.org/10.1016/j.resinv.2021.01.002DOI Listing
February 2021

Primary Tumor Resection Plus Chemotherapy Versus Chemotherapy Alone for Colorectal Cancer Patients With Asymptomatic, Synchronous Unresectable Metastases (JCOG1007; iPACS): A Randomized Clinical Trial.

J Clin Oncol 2021 Apr 9;39(10):1098-1107. Epub 2021 Feb 9.

National Cancer Center Hospital, Tokyo, Japan.

Purpose: It remains controversial whether primary tumor resection (PTR) before chemotherapy improves survival in patients with colorectal cancer (CRC) with asymptomatic primary tumor and synchronous unresectable metastases.

Patients And Methods: This randomized phase III study investigated the superiority of PTR followed by chemotherapy versus chemotherapy alone in relation to overall survival (OS) in patients with unresectable stage IV asymptomatic CRC and three or fewer unresectable metastatic diseases confined to the liver, lungs, distant lymph nodes, or peritoneum. Chemotherapy regimens of either mFOLFOX6 plus bevacizumab or CapeOX plus bevacizumab were decided before study entry. The primary end point was OS, which was analyzed by intention-to-treat.

Results: Between June 2012 and September 2019, a total of 165 patients were randomly assigned to either chemotherapy alone (84 patients) or PTR plus chemotherapy (81 patients). When the first interim analysis was performed in September 2019 with 50% (114/227) of the expected events observed among 160 patients at the data cutoff date of June 5, 2019, the Data and Safety Monitoring Committee recommended early termination of the trial because of futility. With a median follow-up of 22.0 months, median OS was 25.9 months (95% CI, 19.9 to 31.5) in the PTR plus chemotherapy arm and 26.7 (95% CI, 21.9 to 32.5) in the chemotherapy-alone arm (hazard ratio, 1.10; 95% CI, 0.76 to 1.59; one-sided = .69). Three postoperative deaths occurred in the PTR plus chemotherapy arm.

Conclusion: Given that PTR followed by chemotherapy showed no survival benefit over chemotherapy alone, PTR should no longer be considered a standard of care for patients with CRC with asymptomatic primary tumors and synchronous unresectable metastases.
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http://dx.doi.org/10.1200/JCO.20.02447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078424PMC
April 2021

Successful management of heart failure 45 years after surgical correction of tetralogy of Fallot.

J Cardiol Cases 2021 Feb 20;23(2):76-79. Epub 2020 Oct 20.

Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

A 59-year-old Japanese woman was admitted with heart failure due to severe pulmonary regurgitation and tricuspid regurgitation, in addition to atrial fibrillation 45 years after surgical correction of tetralogy of Fallot (TOF). She had been under treatment with medication and catheter ablation for arrhythmia including ventricular tachycardia for the past 28 years. She underwent pulmonary valve replacement as well as tricuspid and mitral valvuloplasty, which obviously improved her status even though her right ventricular end-diastolic volume index exceeded the recommended threshold. Patients who have undergone surgical correction of TOF need to be managed over the long term. < For a long term after surgical correction of tetralogy of Fallot (TOF), appropriate managements are needed for arrhythmia and heart failure related to heart valve disease. Even though her right ventricular end-diastolic volume index exceeded the recommended threshold by the current published guidelines, re-operation for heart valve diseases improved the present patient. We have to accumulate evidence to make useful guideline of re-operation of TOF in Japan.>.
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http://dx.doi.org/10.1016/j.jccase.2020.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817902PMC
February 2021

Clinical Features of Venous Thromboembolism in Patients With Coronavirus Disease 2019 (COVID-19) in Japan - A Case Series Study.

Circ J 2021 02 20;85(3):309-313. Epub 2021 Jan 20.

Department of Cardiology, Kuwana City Medical Center.

Background: Suspicion that the coronavirus disease 2019 (COVID-19) caused venous thromboembolism (VTE).Methods and Results:We conducted a case series study of 5 VTE patients with COVID-19 in Japan. The median body mass index was 27.7 kg/m, and all patients required mechanical ventilation during hospitalization. Patients were diagnosed as VTE in the intensive care unit (ICU), general ward, and outpatient ward.

Conclusions: The current case series study revealed some clinical features of VTE patients with COVID-19 in Japan, including obese patients and those requiring mechanical ventilation during hospitalization, who should be followed closely for VTE, even after leaving the ICU.
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http://dx.doi.org/10.1253/circj.CJ-20-1302DOI Listing
February 2021

Real-world efficacy of atezolizumab in non-small cell lung cancer: A multicenter cohort study focused on performance status and retreatment after failure of anti-PD-1 antibody.

Thorac Cancer 2021 03 15;12(5):613-618. Epub 2021 Jan 15.

Respiratory Center, Matsusaka Municipal Hospital, Matsusaka, Japan.

Background: Atezolizumab is a programmed death-ligand 1 (PD-L1) targeted monoclonal antibody that inhibits PD-L1 interacting with its receptors PD-1 and B7-1, thereby enhancing anticancer immunity. Some real-world efficacy and safety studies of anti-PD-1 antibody have been previously reported. However, there have been no reports investigating the efficacy of atezolizumab monotherapy in clinical practice which have focused on performance status and previous anti-PD-1 antibody treatment.

Methods: We retrospectively reviewed consecutive advanced NSCLC patients who received atezolizumab monotherapy between April 2018 and February 2019 at eight institutions. A total of 152 patients with NSCLC were enrolled in this study.

Results: A total of 38 patients (25%) had already been treated with anti-PD-1 treatment (nivolumab or pembrolizumab) before atezolizumab. The median OS and TTF was 384 days (12.8 months) (95% confidence interval [CI]: 206-424), and 42 days (1.4 months) (95% CI: 27-56) in all patients, respectively. ECOG PS 0 had significantly longer OS (median OS; not reached, p < 0.0001) and TTF (median TTF; 63 days, p = 0.012) compared with PS 1 or 2-3. Most retreated patients were unable to continue atezolizumab for a longer period, but seven patients (18.4%) were able to continue atezolizumab over four months as an ICI retreatment.

Conclusions: In previously treated advanced NSCLC patients, atezolizumab monotherapy demonstrated good efficacy and safety regardless of heavily treated patients in real-world clinical practice, and ECOG PS 0 was a favorable predictive factor. The efficacy of retreatment with atezolizumab was limited but was well tolerated in patients treated with prior anti-PD-1 antibody.
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http://dx.doi.org/10.1111/1759-7714.13824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919123PMC
March 2021

Pulmonary atherosclerosis in a patient with chronic thromboembolic pulmonary hypertension.

Pathol Int 2021 Feb 14;71(2):164-166. Epub 2020 Dec 14.

Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

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http://dx.doi.org/10.1111/pin.13051DOI Listing
February 2021

Tumor Thrombus of Sacral Osteosarcoma Under Inferior Vena Cava Filter.

Circ J 2021 Jan 11;85(2):222. Epub 2020 Dec 11.

Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences.

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http://dx.doi.org/10.1253/circj.CJ-20-1073DOI Listing
January 2021

Serum soluble Klotho is inversely related to coronary artery calcification assessed by intravascular ultrasound in patients with stable coronary artery disease.

J Cardiol 2021 Jun 7;77(6):583-589. Epub 2020 Dec 7.

Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Background: Although the Klotho gene is recognized as an aging-suppressor gene, the clinical significance of its soluble product, soluble Klotho, in coronary artery disease (CAD) has not been completely determined. The relationship between soluble Klotho and coronary artery calcification (CAC) was investigated in patients with stable CAD.

Methods: CAC in culprit lesions was analyzed in 75 non-dialysis patients with stable CAD who were scheduled for percutaneous coronary intervention (PCI) following intravascular ultrasound (IVUS). The main outcome measure was the calcium index (CalcIndex), a volumetric IVUS-derived measure of total calcification per culprit lesion. A low CalcIndex was defined as a first-quartile calcium index (<0.042). Patients were divided into two groups according to the median serum Klotho value: low Klotho (n = 37, ≤460 pg/mL) and high Klotho (n = 38, >460 pg/mL).

Results: The CalcIndex was significantly lower in patients with high than with low Klotho. Patients with high Klotho had a significantly higher prevalence of a low CalcIndex than those with low Klotho. The number of angiographic moderate-severe CACs in whole coronary arteries was significantly decreased in patients with high Klotho compared to low Klotho. Serum Klotho levels correlated significantly and inversely with the CalcIndex. This relationship was pronounced in patients with estimated glomerular filtration rate <60 mL/min/1.73 m. Logistic regression analysis showed that high Klotho was associated with a low CalcIndex independent of classical coronary risk factors and markers of mineral metabolism.

Conclusions: High serum soluble Klotho levels are associated with a low degree of CAC in non-dialysis, stable CAD patients treated by PCI.
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http://dx.doi.org/10.1016/j.jjcc.2020.11.014DOI Listing
June 2021

Aortic Stiffness Is Associated with Coronary Microvascular Dysfunction in Patients with Non-obstructive Coronary Artery Disease.

Intern Med 2020 1;59(23):2981-2987. Epub 2020 Dec 1.

Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Japan.

Objective Associations between aortic stiffness and cardiovascular disease events are mediated in part by pathways that include coronary microvascular dysfunction (CMD) and remodeling. However, the relationship between aortic stiffness and CMD remains unclear. The present study aimed to determine whether aortic stiffness causes CMD as evaluated by the hyperemic microvascular resistance index (hMVRI) in patients with non-obstructive coronary artery disease (CAD). Methods The intracoronary physiological variables in 209 coronary arteries were evaluated in 121 patients with non-obstructive CAD (fractional flow reserve >0.80) or reference vessels. The cardio-ankle vascular index (CAVI) as a measure of aortic stiffness and atherosclerotic risk factors were also measured. Results Univariate analyses showed that hMVRI correlated with age (β=0.24, p=0.007), eicosapentaenoic acid (EPA; β=-0.18, p=0.048), EPA/arachidonic acid (AA) (EPA/AA) ratio (β=-0.22, p=0.014) and CAVI (β=0.30, p=0.001). A multivariate regression analysis identified CAVI (β=0.25, p=0.007) and EPA/AA ratio (β=-0.26, SE=0.211, p=0.003) as independent determinants of hMVRI. Conclusion Aortic stiffness may cause CMD in patients with non-obstructive CAD via increased coronary microvascular resistance. Aortic stiffness is associated with CMD which is evaluated as hyperemic microvascular resistance in patients with non-obstructive CAD.
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http://dx.doi.org/10.2169/internalmedicine.5401-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759696PMC
March 2021

Beneficial impact of weight loss on respiratory function in interstitial lung disease patients with obesity.

Respir Investig 2021 Mar 12;59(2):247-251. Epub 2020 Nov 12.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan.

Background: Interstitial lung disease (ILD) patients commonly become obese or overweight due to deteriorated daily living activities and the adverse effects of prednisolone. This study aimed to clarify the effect of weight loss on pulmonary function test (PFT) in ILD patients with obesity.

Methods: Among all consecutive ILD patients with a body mass index (BMI) ≥ 27 kg/m who received nutrition education for improving obesity between June 2014 and December 2018, we retrospectively included patients who successfully decreased their body weight by over 2 kg and underwent follow-up PFT within 6 months. The results of PFT at baseline and follow-up and the level of Krebs von den Lungen-6 (KL-6) were compared.

Results: Eleven patients (5 men and 6 women; median BMI of 34.1 kg/m), were enrolled. For PFT at baseline, the percentages of forced vital capacity (%FVC), functional residual capacity (%FRC), and diffusing capacity of the lung for carbon monoxide (%DLCO) were 69.3%, 59.9%, and 54%, respectively. The median KL-6 was 1035 U/mL. The median interval from baseline to the follow-up PFTs was 41 days. Compared to the baseline results of PFT, %FVC, %FRC, and %DLCO significantly increased (p = 0.018, 0.0006, and 0.024, respectively), and the changes in body weight and FVC were strongly correlated (p = 0.0004). In addition, the median serum level of KL-6 at follow-up tended to decrease by 206.5 U/mL (p = 0.083).

Conclusion: In ILD patients with obesity, weight loss is important and potentially improves their disease course.
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http://dx.doi.org/10.1016/j.resinv.2020.10.002DOI Listing
March 2021

Febuxostat, a Xanthine Oxidase Inhibitor, Decreased Macrophage Matrix Metalloproteinase Expression in Hypoxia.

Biomedicines 2020 Nov 3;8(11). Epub 2020 Nov 3.

Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto, Nagasaki 852-8501, Japan.

Macrophages in the atheroma region produce matrix metalloproteinases (MMPs) and decrease plaque stability. Tissue oxygen tension decreases in the arterial wall of the atherosclerotic region. Hypoxia inducible factor (HIF)-1α plays a critical role in the transcriptional activation of hypoxia inducible genes. However, the precise roles of HIF-1α independent pathways in hypoxic responses are largely unknown. Xanthine oxidase (XO) is an enzyme that utilizes molecular oxygen and produces reactive oxygen species (ROS). Here, we show that ROS derived from XO increases -3, -10, and -13 expression in murine macrophages. We found that the transcript levels of macrophage -3, -10, and -13 were increased in hypoxic conditions. Hypoxia induced MMP expression in HIF-1α deficient macrophages. -acetylcysteine (NAC) or febuxostat, an XO inhibitor, suppressed MMP expression in murine macrophages. Febuxostat decreased the incidence of plaque rupture in apolipoprotein-E-deficient mice. Our results indicate that febuxostat stabilized atherosclerotic plaque via suppressing the activities of macrophage MMP-9 and -13. Febuxostat administration is a potential therapeutic option in the management of atherosclerotic patients.
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http://dx.doi.org/10.3390/biomedicines8110470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693746PMC
November 2020

Intramyocardial arteriosclerosis with calcification in a patient on haemodialysis due to diabetic nephropathy may not be related to calciphylaxis.

Eur Heart J Case Rep 2020 Jun 21;4(2):1-2. Epub 2020 Feb 21.

Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.

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http://dx.doi.org/10.1093/ehjcr/ytaa031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597417PMC
June 2020

Capecitabine Plus Bevacizumab for Cardiac Metastasis of Sigmoid Colon Cancer: Case Report and Literature Review.

In Vivo 2020 Nov-Dec;34(6):3413-3419

Department of Gastroenterological Surgery, Hiroshima Prefectural Hospital, Hiroshima, Japan.

Background/aim: Right ventricular cardiac metastasis from colorectal cancer (CRC) is rare and clinically silent. There is no standardised treatment. To date, only twelve cases have been reported in the literature. This is a case report and literature review of right ventricular cardiac metastasis from CRC.

Case Report: A 75-year-old woman with a history of CRC treated with sigmoidectomy followed by liver and lung metastasectomy presented with a right ventricle tumour. Biopsy showed metastatic adenocarcinoma not suitable for resection because multiple lung metastases coexisted. The metastases were controlled for a prolonged duration by chemotherapy with capecitabine plus bevacizumab. According to the review of 13 cases, the median age of metastatic CRC that involves the right ventricle is 71 years and the primary site is half the colon and rectum. Half of cases have non-cardiac metastases at cardiac metastasis diagnosis. Chemotherapy is more suitable than resection in cases with metastases other than heart because resection of the right ventricle has a high risk.

Conclusion: Cardiac right ventricular metastasis from CRC can be controlled by capecitabine plus bevacizumab.
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http://dx.doi.org/10.21873/invivo.12180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811651PMC
June 2020

Evaluation of lymphocytic infiltration in the bronchial glands of Sjögren's syndrome in transbronchial lung cryobiopsy.

BMC Pulm Med 2020 Oct 23;20(1):277. Epub 2020 Oct 23.

Department of Respiratory medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-Higashi, Kanazawa-ku, Yokohama city, Kanagawa, 236-0051, Japan.

Background: Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by deteriorated exocrine gland function with associated lymphocytic infiltration. However, there are few pathological studies on bronchial glands in SS. In this study, we aimed to clarify pathological features of bronchial glands in SS.

Methods: We retrospectively evaluated infiltration of lymphocytes in the bronchial glands incidentally collected by transbronchial lung cryobiopsy (TBLC), which were performed for the diagnosis of diffuse lung diseases. The degrees of lymphocyte infiltration in the bronchial glands were classified into four grades (grade 0-3). We compared the degrees of infiltration of SS with those of other diffuse lung diseases.

Results: TBLC for diagnosis of diffuse lung diseases were performed on 432 cases during the study period. The samples of 50 cases included bronchial glands. Of those, 20 cases were excluded due to insufficient size or influence of therapy. The remaining 30 cases included 17 of idiopathic interstitial pneumonias, 5 of chronic hypersensitivity pneumonia, 6 of connective tissue disease (SS; n = 4, systemic sclerosis; n = 1, dermatomyositis; n = 1) and 2 of other diseases. In SS, infiltration of lymphocytes was observed in all cases; grade 1 in one, grade 2 in one, and grade 3 in two cases. In contrast, 11 of 26 in other diseases showed no lymphocytes infiltration, with the remaining 15 of grade 1 infiltration. Grade 2 or more infiltration were found only in SS but not in other diseases.

Conclusion: Our results suggested that high-grade lymphocytic infiltration of bronchial glands is a distinct characteristics in SS.
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http://dx.doi.org/10.1186/s12890-020-01318-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585306PMC
October 2020

Pneumothorax in a COVID-19 Pneumonia Patient without Underlying Risk Factors.

Intern Med 2020 Nov 7;59(22):2921-2925. Epub 2020 Oct 7.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan.

Coronavirus disease 2019 (COVID-19) has been recognized as a worldwide pandemic. However, the clinical course of COVID-19 remains poorly characterized. Although some cases of pneumothorax have been reported, they all had pulmonary complications or were managed with mechanical ventilation. We herein report a case of pneumothorax that developed even though the patient had no pulmonary underlying diseases and had never been managed with mechanical ventilation. In the present case, a lung bulla was found on chest computed tomography during treatment for COVID-19. We concluded that COVID-19 affected the formation of the lung bulla and induced the complication of pneumothorax.
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http://dx.doi.org/10.2169/internalmedicine.5731-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725644PMC
November 2020

Ischemic heart disease cause of intradialytic hypertension in a patient with diabetic nephropathy.

J Cardiol Cases 2020 Oct 2;22(4):181-183. Epub 2020 Jul 2.

Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

A 73-year-old Japanese man was admitted with extreme intradialytic hypertension of four months' duration that was refractory to antihypertensive agents. He had started hemodialysis five years previously because of diabetic nephropathy. Coronary angiography revealed coronary artery disease with significant stenosis of the left main trunk and the right coronary artery, and he underwent a coronary artery bypass graft. Thereafter, the intradialytic hypertension disappeared. Ischemic heart disease appears to be one cause of intradialytic hypertension. < Intradialytic hypertension occurs in some patients with hemodialysis. Such patients are at increased risk for mortality and adverse cardiovascular events. Although the pathophysiological mechanisms remain unknown, ischemic heart disease appears to be one cause of intradialytic hypertension.>.
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http://dx.doi.org/10.1016/j.jccase.2020.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520537PMC
October 2020

Acute thrombosis of everolimus-eluting platinum chromium stent caused by impaired prasugrel metabolism due to cytochrome P450 enzyme 2B6*2 (C64T) polymorphism: a case report.

Eur Heart J Case Rep 2020 Aug 25;4(4):1-7. Epub 2020 Jul 25.

Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.

Background: Dual antiplatelet therapy with aspirin and P2Y12 receptor inhibitor is an important option for preventing acute stent thrombosis after percutaneous coronary intervention (PCI).

Case Summary: A 72-year-old man was admitted to our hospital with ST-segment elevation myocardial infarction. Emergent coronary angiography identified the occlusion in the proximal left anterior descending artery. This lesion was successfully treated by thrombus aspiration and an everolimus-eluting platinum chromium stent implantation with loading of aspirin 200 mg and prasugrel 20 mg. However, acute closure of the stent occurred 1 h after PCI. P2Y12 reaction units (PRU) measured using VerifyNow assay was 282, suggesting high platelet reactivity on prasugrel. After adding cilostazol 200 mg, recanalization was successfully obtained by thrombus aspiration and ballooning under intra-aortic balloon pump. Thereafter, PRU decreased to 266 at 4 h after PCI, and 49 the next day, implying full inhibition of platelet reactivity on prasugrel. Fortunately, no stent thrombosis has recurred since then. Genotype analysis of cytochrome P450 enzyme (CYP) demonstrated CYP2B6*1/*2 polymorphism leading to impaired metabolism of prasugrel. Based on these findings, acute stent thrombosis in the present case might have been caused by delayed expression of prasugrel effects due to CYP2B6*2 (C64T) polymorphism.

Discussion: In cases of stent thrombosis, we should consider the possibility of poor response to P2Y12 receptor inhibitors due to CYP polymorphism. Assessment of platelet aggregation and CYP genotype may be warranted.
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http://dx.doi.org/10.1093/ehjcr/ytaa137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501903PMC
August 2020

How to Safely Prevent Venous Thromboembolism in Severe Trauma Patients.

Int Heart J 2020 Sep 12;61(5):993-998. Epub 2020 Sep 12.

Acute and Critical Care Center, Nagasaki University Hospital.

Venous thromboembolism (VTE) is a life-threatening complication after trauma. Several studies have reported VTE prophylaxis using low-molecular-weight heparin; however, there is no consensus for prophylaxis after trauma. This study aimed to assess the efficacy and safety of our new anticoagulation therapy protocol using unfractionated heparin (UFH) plus intermittent pneumatic compression (IPC) to prevent post-traumatic VTE in high-risk trauma patients.This study enrolled 70 trauma patients who were admitted to the emergency medical center of Nagasaki University Hospital and had Risk Assessment Profile (RAP) scores ≥ 5. After stopping bleeding at the trauma site, all patients received intravenous UFH (10,000 U/day) plus IPC, which was continued for 14 days or until the patients could walk. On days 7 and 14, all patients underwent lower extremity sonography for deep-vein thrombosis screening. VTE incidences between patients with the above intervention and historical controls with IPC alone were compared.No significant differences in age, sex, and the RAP score were observed between the 105 controls and intervention patients. VTE occurrence was fewer in patients with the intervention (14.3%) than in the controls (28.6%; P = 0.029). No hemorrhagic complications occurred after UFH administration. Multivariable logistic analysis revealed a significant association between the intervention and low incidence of VTE (odds ratio: 0.390; 95% confidence interval: 0.163-0.913; P = 0.030).Routine UFH administration with IPC may prevent post-traumatic VTE without adverse events.
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http://dx.doi.org/10.1536/ihj.20-153DOI Listing
September 2020

Randomized, Open-Label, Cross-Over Comparison of the Effects of Benzbromarone and Febuxostat on Endothelial Function in Patients with Hyperuricemia.

Int Heart J 2020 Sep 12;61(5):984-992. Epub 2020 Sep 12.

Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences.

Uric acid is generated with reactive oxygen species via xanthine oxidase (XO), and hyperuricemia, which is identified as the excess of uric acid in the blood, has been associated with vascular endothelial dysfunction. However, the effects of urate-lowering medicines on endothelial function have not been fully elucidated. Thus this study determined and compared the effects of benzbromarone (urate transporter 1 inhibitor) and febuxostat (XO inhibitor) on endothelial function.This randomized, cross-over, open-label study initially recruited 30 patients with hyperuricemia. They were divided into two groups, treated initially with benzbromarone or febuxostat for three months and then were switched for the next three months. Endothelial function was defined as reactive hyperemia indexes (RHI) determined using Endo-PAT 2000 before and at three and six months after medication using the two agents. Blood levels of asymmetric dimethylarginine (ADMA) and high-molecular-weight (HMW) adiponectin were also compared. We finally analyzed data from 24 patients whose endothelial function was assessed as described above.Our findings show that levels of uric acid significantly decreased, whereas those of HMW adiponectin and the RHI have significantly increased after treatment with benzbromarone. Meanwhile, in patients administered with febuxostat, uric acid levels tended to decrease and RHI significantly decreased. Neither of the two agents altered ADMA levels. The changes in RHI (P = 0.026) and HMW adiponectin levels (P = 0.001) were found to be significantly greater in patients treated with benzbromarone than febuxostat. Changes in the levels of HMW adiponectin and of uric acid were significantly correlated (r = -0.424, P = 0.039).Benzbromarone has increased adiponectin besides reducing uric acid levels, and thus, this might confer more benefits on endothelial function than febuxostat.
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http://dx.doi.org/10.1536/ihj.20-114DOI Listing
September 2020

Outcome of early-stage combination treatment with favipiravir and methylprednisolone for severe COVID-19 pneumonia: A report of 11 cases.

Respir Investig 2020 Aug 28. Epub 2020 Aug 28.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan. Electronic address:

Although the use of corticosteroids is not recommended in the World Health Organization statement for the treatment of coronavirus disease 2019 (COVID-19), steroid therapy may be indicated for critical cases in specific situations. Here, we report the successful treatment of 11 cases of severe COVID-19 pneumonia with favipiravir and methylprednisolone. All cases were severe and patients required oxygen administration or had a blood oxygen saturation ≤93% on room air. All were treated with favipiravir and methylprednisolone, and 10 of 11 patients responded well and required no further oxygen supplementation or ventilator management. This study shows the importance of the early-stage use of a combination of favipiravir and methylprednisolone in severe cases to achieve a favorable clinical outcome.
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http://dx.doi.org/10.1016/j.resinv.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455106PMC
August 2020

Tolerability and safety of nintedanib in elderly patients with idiopathic pulmonary fibrosis.

Respir Investig 2021 Jan 3;59(1):99-105. Epub 2020 Sep 3.

Kanagawa Cardiovascular and Respiratory Center, Department of Respiratory Medicine, Tomioka-Higashi 6-16-1, Kanazawa-ku, Yokohama, 236-0051, Japan. Electronic address:

Background: In the phase III trial of nintedanib, only 10.8% of participants were aged ≥75 years. Here, we aimed to evaluate the tolerability and safety of nintedanib in elderly patients with idiopathic pulmonary fibrosis (IPF).

Methods: In total, 71 consecutive patients with (1) IPF, (2) age ≥75 years, and (3) newly prescribed nintedanib from September 2015 to April 2018 (elderly group) were retrospectively reviewed. Patient characteristics, treatment status, and adverse events (AEs) were compared between the elderly group and 126 patients with IPF, aged <75 years, with newly prescribed nintedanib during the same period (non-elderly group).

Results: In the elderly group, 32 patients (46.4%) discontinued nintedanib within 6 months. Body size was significantly smaller, the incidence rates of anorexia and nausea were significantly higher, and early termination within 6 months were more common in the elderly than in the non-elderly group. In elderly patients, a univariate logistic regression analysis showed that body mass index (BMI) and percentage forced vital capacity (FVC) were risk factors for early termination (p = 0.02 and 0.03, respectively). A low initial nintedanib dose did not reduce the incidence of AEs and early termination rate in the elderly group.

Conclusions: In elderly patients with IPF, the incidence of early nintedanib termination was higher, and anorexia and nausea were common AEs compared with those in non-elderly IPF patients. Treatment was frequently discontinued in elderly patients with low BMI and FVC, and chest physicians should be aware that nintedanib therapy may result in early termination in these patients.
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http://dx.doi.org/10.1016/j.resinv.2020.08.003DOI Listing
January 2021

[A Survey of Relationships Between Job Stressors, Degree of Mental Health, Organizational Climate and the Identity of Newly Graduated Nurses].

J UOEH 2020 ;42(3):281-290

Graduate School of Nursing, Fukuoka Prefectural University, Japan.

The purpose of this study is to investigate and clarify the relationships between occupational stress, personal factors, buffer factors and stress responses of newly graduated nurses, based on the NIOSH model. A questionnaire survey was conducted on 320 newly graduated nurses working at university hospitals where research cooperation was obtained. Data from 107 people was collected by mail (the response rate of 33.4%). In the results of the analysis, the GHQ-12 scores of the nurses on the three-shift system (23.5 ± 7.04) were found to be higher than those on the two-shift system (18.88 ± 6.03) (P = 0.007). The GHQ-12 score was significantly higher in the high stressor group (24.1 ± 6.20), who had higher job demand and lower work ratings than the low stressor group (18.93 ± 6.14) (P = 0.001, t = -3.44). The results of a multiple logistic regression analysis using high/low GHQ groups defined by a cut-off point of 4 in the GHQ-12 (GHQ method) as the dependent variables and the associated variables as the independent variables showed that the basic role identity and colleague support were found to have a significant relationship. The results of a Hosmer-Lemeshow test were P = 0.643, and the coefficient of determination was as high as 81.0%. This study was conducted approximately 6 months after the nurses entered employment, which is in the middle of the critical transition period from a student to a working member of society and can be assumed to be the most exhausting state of the year both physically and mentally. The results of this study suggest that various stressors might cause serious stress reactions. Also, as shown in previous literature, newly graduated nurses tend not to seek support from their bosses or preceptors throughout the year. Their main sources of support are family members, friends, and colleagues. Taken together, it became clear from our study that support from colleagues in the workplace is the most powerful buffer against stress and an indispensable resource to overcome the "reality shock" of working life.
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http://dx.doi.org/10.7888/juoeh.42.281DOI Listing
September 2020

Selexipag for Chronic Thromboembolic Pulmonary Hypertension in Japanese Patients - A Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase II Study.

Circ J 2020 09 3;84(10):1866-1874. Epub 2020 Sep 3.

Kuriyama Clinic.

Background: Selexipag is an oral prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. This study examined its efficacy and safety in Japanese patients with non-operated or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH).Methods and Results:This Phase II study was a randomized, double-blind, placebo-controlled parallel-group comparison. The primary endpoint was a change in pulmonary vascular resistance (PVR) from baseline to week 17. The main analysis involved a per-protocol set group of 28 subjects. The change in PVR (mean±SD) after 17 weeks of treatment in the selexipag group was -104±191 dyn·s/cm, whereas that in the placebo group was 26±180 dyn·s/cm. Thus, the treatment effect after 17 weeks of selexipag treatment was calculated as -130±189 dyn·s/cm(P=0.1553). Although the primary endpoint was not met, for the group not concomitantly using a pulmonary vasodilator the PVR in the selexipag group was significantly decreased compared with placebo group (P=0.0364). The selexipag group also showed improvement in total pulmonary resistance and cardiac index.

Conclusions: Selexipag treatment improved pulmonary hemodynamics in Japanese patients with CTEPH, but PVR did not show a significant difference between the selexipag and placebo groups. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-111667]).
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http://dx.doi.org/10.1253/circj.CJ-20-0438DOI Listing
September 2020