Faculty Profiles - IMAIZUMI Takahiro

Papers - IMAIZUMI Takahiro

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Excess risk of cardiovascular events in patients in the United States vs. Japan with chronic kidney disease is mediated mainly by left ventricular structure and function

Imaizumi, T; Fujii, N; Hamano, T; Yang, W; Taguri, M; Kansal, M; Mehta, R; Shafi, T; Taliercio, J; Go, A; Rao, PDRA; Hamm, LL; Deo, R; Maruyama, S; Fukagawa, M; Feldman, HI

KIDNEY INTERNATIONAL Vol. 103 ( 5 ) page： 949 - 961 2023.5

Language：English Publisher：Kidney International

While patients receiving dialysis therapy in the United States are more likely to develop cardiovascular disease (CVD) than those in Japan, direct comparisons of patients with predialysis chronic kidney disease (CKD) are rare. To study this, we compared various outcomes in patients with predialysis CKD using data from the Chronic Renal Insufficiency Cohort (CRIC) and CKD Japan Cohort (CKD-JAC) studies and determined mediators of any differences. Candidate mediators included left ventricular (LV) indices assessed by echocardiography. Among 3125 CRIC and 1097 CKD-JAC participants, the mean LV mass index (LVMI) and ejection fraction (EF) were 55.7 and 46.6 g/m2 and 54% and 65%, respectively (both significant). The difference in body mass index (32 and 24 kg/m2, respectively) largely accounted for the differences in LVMI and C-reactive protein levels across cohorts. Low EF and high LVMI were significantly associated with subsequent CVD in both cohorts. During a median follow-up of five years, CRIC participants were at higher risk for CVD (adjusted hazard ratio [95% confidence interval]: 3.66 [2.74–4.89]) and death (4.69 [3.05–7.19]). A three-fold higher C-reactive protein concentration and higher phosphate levels in the United States cohort were moderately strong mediators of the differences in CVD. However, echocardiographic parameters were stronger mediators than these laboratory measures. LVMI, EF and their combination mediated the observed difference in CVD (27%, 50%, and 57%, respectively) and congestive heart failure (33%, 62%, and 70%, respectively). Thus, higher LV mass and lower EF, even in the normal range, were found to be predictive of CVD in CKD.

DOI： 10.1016/j.kint.2023.01.008

Fibcare® shows correlation with fibrinogen levels by the Clauss method during cardiopulmonary bypass

Yamada, A; Tamura, T; Imaizumi, T; Kubo, Y; Nishiwaki, K

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 85 ( 2 ) page： 310 - 318 2023.5

Language：English Publisher：Nagoya Journal of Medical Science

Central laboratory measurements are time consuming, while rapid fibrinogen level measurements within the operating room improve transfusion strategies. We aimed to clarify the correlation between fibrinogen concentrations (measured using Fibcare® and the Clauss fibrinogen assay in a central laboratory) during cardiovascular surgery with cardiopulmonary bypass. Data of patients whose Fibcare, traditional laboratory-based testing, and thromboelastographic results were measured using the same blood sample during cardiopulmonary bypass from February 2021 to January 2022 were retrospectively examined. We analyzed correlation in categories of body temperature during cardiopulmonary bypass: total cases, mild hypothermia (28–34°C), and moderate or severe hypothermia (<28°C). The Clauss fibrinogen assay was performed in 123 cases, Fibcare in 107, and thromboelastography in 91. For mild hypothermia, moderate or severe hypothermia, and overall, the root mean squared error and R-square in Fibcare were 16.1 and 0.86, 13.1 and 0.87, and 14.9 and 0.87, respectively, and for thromboelastography, they were 3.26 and 0.74, 2.70 and 0.79, and 3.08 and 0.75, respectively. A significant relationship was noted between Fibcare and Claus fibrinogen analysis regardless of body temperature during cardiopulmonary bypass. The measurement of fibrinogen levels using Fibcare allows for faster transfusion preparation than that of the traditional Clauss fibrinogen assay.

DOI： 10.18999/nagjms.85.2.310

Machine learning models predict delayed hyponatremia post-transsphenoidal surgery using clinically available features

Fuse, Y; Takeuchi, K; Nishiwaki, H; Imaizumi, T; Nagata, Y; Ohno, K; Saito, R

PITUITARY Vol. 26 ( 2 ) page： 237 - 249 2023.4

Language：English Publisher：Pituitary

Purpose: Delayed hyponatremia (DHN), a unique complication, is the leading cause of unexpected readmission after pituitary surgery. Therefore, this study aimed to develop tools for predicting postoperative DHN in patients undergoing endoscopic transsphenoidal surgery (eTSS) for pituitary neuroendocrine tumors (PitNETs). Methods: This was a single-center, retrospective study involving 193 patients with PitNETs who underwent eTSS. The objective variable was DHN, defined as serum sodium levels < 135 mmol/L at ≥ 1 time between post operative days 3 and 9. We trained four machine learning models to predict this objective variable using the clinical variables available preoperatively and on the first postoperative day. The clinical variables included patient characteristics, pituitary-related hormone levels, blood test results, radiological findings, and postoperative complications. Results: The random forest (RF) model demonstrated the highest (0.759 ± 0.039) area under the curve of the receiver operating characteristic curve (ROC-AUC), followed by the support vector machine (0.747 ± 0.034), the light gradient boosting machine (LGBM: 0.738 ± 0.026), and the logistic regression (0.710 ± 0.028). The highest accuracy (0.746 ± 0.029) was observed in the LGBM model. The best-performing RF model was based on 24 features, nine of which were clinically available preoperatively. Conclusions: The proposed machine learning models with pre- and post-resection features predicted DHN after the resection of PitNETs.

DOI： 10.1007/s11102-023-01311-w

Effectiveness of tacrolimus concomitant with biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis

Terabe, K; Takahashi, N; Asai, S; Hirano, Y; Kanayama, Y; Yabe, Y; Oguchi, T; Fujibayashi, T; Ishikawa, H; Hanabayashi, M; Hattori, Y; Suzuki, M; Kishimoto, K; Ohashi, Y; Imaizumi, T; Imagama, S; Kojima, T

MODERN RHEUMATOLOGY Vol. 33 ( 2 ) page： 292 - 301 2023.3

Language：English Publisher：Modern rheumatology

OBJECTIVES: The study aimed to investigate the effectiveness and tolerance of biological disease-modifying antirheumatic drugs (bDMARDs) therapy administered concomitantly with tacrolimus (TAC) treatment in patients with rheumatoid arthritis. METHODS: 2792 patients who underwent therapy with five bDMARDs (etanercept: ETN, adalimumab, golimumab, tocilizumab, and abatacept: ABT) were enrolled. Among the study subjects, 1582 were concomitant methotrexate (MTX group), 147 were concomitant TAC (TAC group), and 1063 were non-concomitant MTX and TAC (non-MTX/TAC group). The primary outcome was the incident rate of discontinuation of bDMARDs by adverse events (AEs) or loss of efficacy. RESULTS: Concerning the analysis for each reasons of discontinuation, including AEs and loss of efficacy, the hazards ratio (HR) was significantly lower in the TAC group than in non-MTX/TAC groups (AEs: HR = 0.39, 95% confidence interval, 0.23-0.68, loss of efficacy: HR = 0.49, 95% confidence interval, 0.30-0.78). The loss of efficacy with the use of ETN and ABT was lower in the TAC group than in non-MTX/TAC groups. Concomitant TAC did not induce elevated risk for discontinuation of AEs in all bDMARD analyses. CONCLUSIONS: Concomitant TAC with ABT or ETN showed higher retention rates than bDMARDs therapy without TAC or MTX. AEs did not increase over long-term observation.

DOI： 10.1093/mr/roac025

Prevalence and Risk Factors of Insomnia and Sleep-aid Use in Emergency Physicians in Japan: Secondary Analysis of a Nationwide Survey

Chiba, T; Hagiwara, Y; Hifumi, T; Kuroda, Y; Ikeda, S; Khoujah, D; Imaizumi, T; Shiga, T

WESTERN JOURNAL OF EMERGENCY MEDICINE Vol. 24 ( 2 ) page： 331 - 339 2023.3

Language：English Publisher：Western Journal of Emergency Medicine

Introduction: Emergency physicians (EP) are suspected to have a high prevalence of insomnia and sleep-aid use. Most prior studies about sleep-aid use in EPs have been limited by low response rates. In this study our aim was to investigate the prevalence of insomnia and sleep-aid use among early-career Japanese EPs and assess the factors associated with insomnia and sleep-aid use. Methods: We collected anonymous, voluntary, survey-based data regarding chronic insomnia and sleep-aid use from board-eligible EPs taking the initial Japanese Association of Acute Medicine board certification exam in 2019 and 2020. We describe the prevalence of insomnia and sleep-aid use and analyzed demographic and job-related factors using multivariable logistic regression analysis. Results: The response rate was 89.71% (732 of 816). The prevalence of chronic insomnia and sleep-aid use was 24.89% (95% CI 21.78-28.29%) and 23.77% (95% CI 20.69-27.15%), respectively. Factors associated with chronic insomnia were long working hours (odds ratio [OR] 1.02, 1.01-1.03, per one-hour/week), and “stress factor” (OR 1.46, 1.13-1.90). Factors associated with sleep-aid use were male gender (OR 1.71, 1.03-2.86), unmarried status (OR 2.38, 1.39-4.10), and “stress factor” (OR 1.48, 1.13-1.94). The “stress factor” was mostly influenced by stressors in dealing with patients/families and co-workers, concern about medical malpractice, and fatigue. Conclusions: Early-career EPs in Japan have a high prevalence of chronic insomnia and sleep-aid use. Long working hours and stress were associated with chronic insomnia, while male gender, unmarried status, and stress were associated with the use of sleep aids.

DOI： 10.5811/westjem.2022.12.57910

Impact of guideline recommendation for novel surgical procedures on surgeons' decisions: a time series analysis of gastric cancer surgeries from a nationwide cohort study

Honda, M; Yasunaga, H; Michihata, N; Miyakawa, T; Kumazawa, R; Matsui, H; Imaizumi, T

INTERNATIONAL JOURNAL OF SURGERY Vol. 109 ( 3 ) page： 316 - 322 2023.3

Language：English Publisher：International journal of surgery (London, England)

BACKGROUND: Since two Japanese guidelines, for gastric cancer treatment and for minimally invasive surgery, were simultaneously revised in 2014, laparoscopic distal gastrectomy has been a standard procedure for clinical stage I gastric cancer. MATERIALS AND METHODS: We evaluated the impact of this revision on surgeons' decision-making using a nationwide inpatient database in Japan. We described the time trends in the proportion of laparoscopic surgery from January 2011 to December 2018. We performed an interrupted time series analysis; the exposure time point was August 2014, and the main outcome was the change in slope before and after the revision of the guidelines. We performed a subgroup analysis of hospital volume and the odds ratio (OR) for postoperative complications according to exposure. RESULTS: A total of 64 910 patients who underwent subtotal gastrectomy for stage I disease were identified. During the study period, the proportion of laparoscopic surgery showed a consistent increase from 47.4 to 81.2%. After the revision, the slope of the increase was rather slow; the OR [95% CI] was 0.601 [0.548-0.654] before the revision and 0.219 [0.176-0.260] after the revision. The adjusted ORs were 0.642 [0.575-0.709] before the revision and 0.240 [0.187-0.294] after the revision. CONCLUSION: The revision of the guidelines recommending laparoscopic surgery had little impact on surgeons' decisions regarding the choice of procedure.

DOI： 10.1097/JS9.0000000000000179

Biopsy-proven CKD etiology and outcomes: the Chronic Kidney Disease Japan Cohort (CKD-JAC) study

Hamano, T; Imaizumi, T; Hasegawa, T; Fujii, N; Komaba, H; Ando, M; Nangaku, M; Nitta, K; Hirakata, H; Isaka, Y; Wada, T; Maruyama, S; Fukagawa, M

NEPHROLOGY DIALYSIS TRANSPLANTATION Vol. 38 ( 2 ) page： 384 - 395 2023.2

Language：English Publisher：Nephrology Dialysis Transplantation

Background: The Kidney Disease: Improving Global Outcomes guidelines advocate the cause-glomerular filtration rate (GFR)-albuminuria (CGA) classification for predicting outcomes. However, there is a dearth of data supporting the use of the cause of chronic kidney disease. This study aimed to address how to incorporate a prior biopsy-proven diagnosis in outcome prediction. Methods: We examined the association of biopsy-proven kidney disease diagnoses with kidney failure with replacement therapy (KFRT) and all-cause death before KFRT in patients with various biopsy-proven diagnoses (n = 778, analysis A) and patients with diabetes mellitus labeled with biopsy-proven diabetic nephropathy (DN), other biopsy-proven diseases and no biopsy (n = 1117, analysis B). Results: In analysis A, adding biopsy-proven diagnoses to the GFR-albuminuria (GA) classification improved the prediction of 8-year incidence of KFRT and all-cause death significantly regarding integrated discrimination improvement and net reclassification index. Fine-Gray (FG) models with KFRT as a competing event showed significantly higher subdistribution hazard ratios (SHRs) for all-cause death in nephrosclerosis {4.12 [95% confidence interval (CI) 1.11-15.2)], focal segmental glomerulosclerosis [3.77 (95% CI 1.09-13.1)]} and membranous nephropathy (MN) [2.91 (95% CI 1.02-8.30)] than in immunoglobulin A nephropathy (IgAN), while the Cox model failed to show significant associations. Crescentic glomerulonephritis had the highest risk of all-cause death [SHR 5.90 (95% CI 2.05-17.0)]. MN had a significantly lower risk of KFRT than IgAN [SHR 0.45 (95% CI 0.24-0.84)]. In analysis B, other biopsy-proven diseases had a lower risk of KFRT than biopsy-proven DN in the FG model, with death as a competing event [SHR 0.62 (95% CI 0.39-0.97)]. Conclusions: The CGA classification is of greater value in predicting outcomes than the GA classification.

DOI： 10.1093/ndt/gfac134

Prognosis in Patients With Cardiogenic Shock Who Received Temporary Mechanical Circulatory Support.

Kondo T, Araki T, Imaizumi T, Sumita Y, Nakai M, Tanaka A, Okumura T, Butt JH, Petrie MC, McMurray JJV, Murohara T

JACC. Asia Vol. 3 ( 1 ) page： 122 - 134 2023.2

Language：English Publisher：JACC: Asia

Background: Temporary mechanical circulatory support (MCS) is often used in patients with cardiogenic shock (CS), and the type of MCS may vary by cause of CS. Objectives: This study sought to describe the causes of CS in patients receiving temporary MCS, the types of MCS used, and associated mortality. Methods: This study used a nationwide Japanese database to identify patients receiving temporary MCS for CS between April 1, 2012, and March 31, 2020. Results: Of 65,837 patients, the cause of CS was acute myocardial infarction (AMI) in 77.4%, heart failure (HF) in 10.9%, valvular disease in 2.7%, fulminant myocarditis (FM) in 2.5%, arrhythmia in 4.5%, and pulmonary embolism (PE) in 2.0% of cases. The most commonly used MCS was an intra-aortic balloon pump alone in AMI (79.2%) and in HF (79.0%) and in valvular disease (66.0%), extracorporeal membrane oxygenation with intra-aortic balloon pump in FM (56.2%) and arrhythmia (43.3%), and extracorporeal membrane oxygenation alone in PE (71.5%). Overall in-hospital mortality was 32.4%; 30.0% in AMI, 32.6% in HF, 33.1% in valvular disease, 34.2% in FM, 60.9% in arrhythmia, and 59.2% in PE. Overall in-hospital mortality increased from 30.4% in 2012 to 34.1% in 2019. After adjustment, valvular disease, FM, and PE had lower in-hospital mortality than AMI: valvular disease, OR: 0.56 (95% CI: 0.50-0.64); FM: OR: 0.58 (95% CI: 0.52-0.66); PE: OR: 0.49 (95% CI: 0.43-0.56); whereas HF had similar in-hospital mortality (OR: 0.99; 95% CI: 0.92-1.05) and arrhythmia had higher in-hospital mortality (OR: 1.14; 95% CI: 1.04-1.26). Conclusions: In a Japanese national registry of patients with CS, different causes of CS were associated with different types of MCS and differences in survival.

DOI： 10.1016/j.jacasi.2022.10.004

Interaction of Blood Pressure and Glycemic Status in Developing Cardiovascular Disease: Analysis of a Nationwide Real-World Database

Suzuki, Y; Kaneko, H; Yano, Y; Okada, A; Itoh, H; Matsuoka, S; Yokota, I; Imaizumi, T; Fujiu, K; Michihata, N; Jo, T; Takeda, N; Morita, H; Node, K; Yasunaga, H; Komuro, I

JOURNAL OF THE AMERICAN HEART ASSOCIATION Vol. 12 ( 1 ) page： e026192 2023.1

Language：English Publisher：Journal of the American Heart Association

BACKGROUND: Hypertension and diabetes frequently coexist. However, little is known about the interaction between high blood pressure (BP) and hyperglycemia in the development of cardiovascular disease (CVD). METHODS AND RESULTS: We conducted an observational cohort study that included 3 336 363 patients (median age, 43 years old; men, 57.2%). People taking BP-or glucose-lowering medications or those with prior history of CVD were excluded. We defined stage 1 hypertension as having systolic BP of 130 to 139 mm Hg or diastolic BP of 80 to 89 mm Hg and stage 2 hypertension as having systolic BP of ≥140 mm Hg or diastolic BP of ≥90 mm Hg. We defined prediabetes as having fasting plasma glucose of 100 to 125 mg/dL and diabetes as having fasting plasma glucose of ≥126 mg/dL. Over a mean follow-up period of 1185 ± 942 days, 5665 myocardial infarction, 52 475 angina pectoris, 25 436 stroke, 54 508 heart failure, and 12 932 atrial fibrillation events occurred. The BP and fasting plasma glucose categories additively increased the risk of myocardial infarc-tion, angina pectoris, stroke, heart failure, and atrial fibrillation. However, the relative risk of stage 1 and stage 2 hypertension developing into CVD was attenuated with deteriorating glycemic status. Similarly, the relative risk of prediabetes and diabetes developing into CVD was attenuated with increasing BP. For example, the relative risk reduction of stage 2 hypertension for heart failure was 53.5% in individuals with normal fasting plasma glucose, 46.4% in those with prediabetes, and 37.2% in those with diabetes. The robustness of our findings was confirmed using a multitude of sensitivity analyses. CONCLUSIONS: Although hypertension and hyperglycemia additively increase the risk of developing CVD, the relative contribution of hypertension to the development of CVD decreased with deteriorating glycemic status and that of hyperglycemia was attenuated with increasing BP. Our results indicate a potential interaction between hypertension and hyperglycemia in the development of CVD.

DOI： 10.1161/JAHA.122.026192

Caregiver Burdens, Health Risks, Coping and Interventions among Caregivers of Dementia Patients: A Review of the Literature

Goto Yasuyuki, Morita Kohei, Suematsu Mina, Imaizumi Takahiro, Suzuki Yusuke

Internal Medicine Vol. 62 ( 20 ) page： 3277 - 3282 2023

Language：English Publisher：The Japanese Society of Internal Medicine

<p>Over 55 million people reportedly suffer from dementia worldwide. In Japan, it is estimated that 1 in 5 people over 65 years old will have dementia by 2025, of which more than 20% will live with symptoms that require home/nursing care. Given the lack of effective medical treatments for dementia, informal caregivers play essential roles in allowing dementia patients to live with dignity. Our review focusing on caregiver burden showed that this burden has not been sufficiently addressed, despite having negative effects on caregivers' health, employment, and finances. It is important to consider non-pharmacological interventions that contribute to effective coping strategies for mitigating the caregiver burden. Online communication tools may be a viable intervention measure to educate caregivers on the importance of sharing resilient coping strategies to reduce their stress so that they can continue to provide care for their loved ones. </p>

DOI： 10.2169/internalmedicine.0911-22

Identifying high-risk population of depression: association between metabolic syndrome and depression using a health checkup and claims database

Imaizumi, T; Toda, T; Maekawa, M; Sakurai, D; Hagiwara, Y; Yoshida, Y; Ando, M; Maruyama, S

SCIENTIFIC REPORTS Vol. 12 ( 1 ) page： 18577 2022.11

Language：English Publisher：Scientific Reports

Depression and metabolic syndrome (MetS) are correlated, leading to an increased healthcare burden and decreased productivity. We aimed to investigate the association between MetS-related factors and depression using a health checkup and claims database. Individuals aged 18–75 years who underwent health examinations between 2014 and 2019 were enrolled in the study. Among 76,277 participants, “ever” and “incident” antidepressant users exhibited worse metabolic profiles and were more likely to be prescribed hypnotics and anxiolytics than “never” users. In a nested case–control study with a 1:10 ratio of incident users to controls, MetS was associated with incident antidepressant use (odds ratio, 1.53 [95% confidence interval 1.24–1.88]) adjusted for lifestyle information obtained from a self-administered questionnaire, medical history, and medications. Other metabolic traits also showed significant associations: body mass index (1.04 [1.02–1.06]), abdominal circumference per 10 cm (1.17 [1.08–1.27]), high blood pressure (1.17 [1.00–1.37]), glucose intolerance (1.29 [1.05–1.58]), and dyslipidemia (1.27 [1.08–1.51]). A bodyweight increase > 10 kg from age 20 years (1.46 [1.25–1.70]) was also significantly associated with incident antidepressant use. In conclusion, metabolic abnormalities were associated with incident antidepressant use and can be useful in identifying populations at high risk of depression.

DOI： 10.1038/s41598-022-22048-9

Current Status of Outpatient Oral Antimicrobial Prescription and the Influence of Antimicrobial Stewardship for Inpatients: A Repeated Cross-Sectional Study at a Japanese Community Hospital

Tsuchimoto Daisuke, Morioka Hiroshi, Imaizumi Takahiro, Miyagawa Sawako, Yamamoto Masashi, Onishi Katsuhiro, Kuwabara Yukinori, Takada Kazuto, Watamoto Koichi

BIOLOGICAL & PHARMACEUTICAL BULLETIN Vol. 45 ( 9 ) page： 1340 - 1346 2022.9

Clinical parameter-based prediction of DNA methylation classification generates a prediction model of prognosis in patients with juvenile myelomonocytic leukemia

Imaizumi, T; Meyer, J; Wakamatsu, M; Kitazawa, H; Murakami, N; Okuno, Y; Yoshida, T; Sajiki, D; Hama, A; Kojima, S; Takahashi, Y; Loh, M; Stieglitz, E; Muramatsu, H

SCIENTIFIC REPORTS Vol. 12 ( 1 ) page： 14753 2022.8

Language：English Publisher：Scientific Reports

Juvenile myelomonocytic leukemia (JMML) is a rare heterogeneous hematological malignancy of early childhood characterized by causative RAS pathway mutations. Classifying patients with JMML using global DNA methylation profiles is useful for risk stratification. We implemented machine learning algorithms (decision tree, support vector machine, and naïve Bayes) to produce a DNA methylation-based classification according to recent international consensus definitions using a well-characterized pooled cohort of patients with JMML (n = 128). DNA methylation was originally categorized into three subgroups: high methylation (HM), intermediate methylation (IM), and low methylation (LM), which is a trichotomized classification. We also dichotomized the subgroups as HM/IM and LM. The decision tree model showed high concordances with 450k-based methylation [82.3% (106/128) for the dichotomized and 83.6% (107/128) for the trichotomized subgroups, respectively]. With an independent cohort (n = 72), we confirmed that these models using both the dichotomized and trichotomized classifications were highly predictive of survival. Our study demonstrates that machine learning algorithms can generate clinical parameter-based models that predict the survival outcomes of patients with JMML and high accuracy. These models enabled us to rapidly and effectively identify candidates for augmented treatment following diagnosis.

DOI： 10.1038/s41598-022-18733-4

Risk factors for unplanned removal of central venous catheters in hospitalized children with hematological and oncological disorders

Miyagishima, M; Hamada, M; Hirayama, Y; Muramatsu, H; Tainaka, T; Shirota, C; Hinoki, A; Imaizumi, T; Nakatochi, M; Kamei, M; Nishikawa, E; Kawashima, N; Narita, A; Nishio, N; Kojima, S; Takahashi, Y

INTERNATIONAL JOURNAL OF HEMATOLOGY Vol. 116 ( 2 ) page： 288 - 294 2022.8

Language：English Publisher：International Journal of Hematology

Central venous catheters (CVCs) are essential devices in the treatment of pediatric patients with hematological and oncological disorders; however, the most suitable type of CVC for these patients remains unclear. We retrospectively compared risk factors for unplanned removal of two commonly used CVCs, peripherally inserted central catheters (PICCs) and tunneled CVCs, to propose which is the better device. We followed 89 patients fitted with a tunneled CVC (total 21,395 catheter-days) and 84 fitted with a PICC (total 9177 catheter-days) between January 1, 2013 and December 31, 2015, until catheter removal. Patients with a PICC had a significantly higher 3-month cumulative incidence of catheter occlusion (5.2% vs. 0%, p = 4.08 × 10−3) and total unplanned removals (29.0% vs. 6.9%, p = 0.0316) than those with tunneled CVCs. However, the cumulative incidence of central line-associated bloodstream infection did not differ significantly by CVC type. Multivariable analysis identified younger age (< 2 years) [sub-distribution hazard ratio (SHR) 2.29; 95% confidence interval (CI) 1.27–4.14] and PICC (SHR 2.73; 95% CI 1.48–5.02) as independent risk factors for unplanned removal. Thus, our results suggest that tunneled CVCs are preferable in pediatric patients with hematological and oncological disorders requiring long-term, intensive treatment.

DOI： 10.1007/s12185-022-03346-4

Association of alcohol consumption with the incidence of proteinuria and chronic kidney disease: a retrospective cohort study in Japan

Tanaka, A; Yamaguchi, M; Ishimoto, T; Katsuno, T; Nobata, H; Iwagaitsu, S; Sugiyama, H; Kinashi, H; Banno, S; Imaizumi, T; Ando, M; Kubo, Y; Ito, Y

NUTRITION JOURNAL Vol. 21 ( 1 ) page： 31 2022.5

Language：English Publisher：Nutrition Journal

Background: The difference in the clinical impact of alcohol consumption on kidney function based on sex remains to be elucidated. This study aimed to assess the association between the dose of alcohol consumption and the incidence of proteinuria and chronic kidney disease stratified by sex. Methods: This retrospective cohort study included 26,788 workers (19,702 men and 7086 women) with normal renal function (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2) at annual health examinations between January 2010 and March 2015 in Japan. The main exposure was alcohol consumption. The primary outcomes were the incidence of proteinuria (dipstick urinary protein ≥ 1) and incidence of low estimated glomerular filtration rate (eGFR; rate < 60 mL/min per 1.73 m2; decreased from the baseline eGFR by 25%). Results: During a median observational period of 4 years (interquartile range: 2–6), 1993 (10.1%) men and 462 (6.5%) women developed proteinuria, whereas 667 (3.4%) men and 255 (3.6%) women developed low eGFR. After adjustment for clinically relevant factors using a Cox proportional hazards model, alcohol consumption of ≥ 46 g/day in females was significantly associated with the incidence of proteinuria (hazard ratio, 1.57; 95% confidence interval, 1.10–2.26) and low eGFR (hazard ratio, 1.62; 95% confidence interval, 1.04–2.53). However, no significant association between alcohol consumption and primary outcomes was observed in men. Conclusions: In conclusion, daily higher alcohol consumption was significantly associated with a higher incidence of proteinuria and low eGFR among women. Women might be prone to high alcohol consumption with kidney dysfunction.

DOI： 10.1186/s12937-022-00785-x

Differences in Prognosis and Cardiac Function According to Required Percutaneous Mechanical Circulatory Support and Histological Findings in Patients With Fulminant Myocarditis: Insights From the CHANGE PUMP 2 Study

Kondo, T; Okumura, T; Shibata, N; Imaizumi, T; Dohi, K; Izawa, H; Ohte, N; Amano, T; Murohara, T

JOURNAL OF THE AMERICAN HEART ASSOCIATION Vol. 11 ( 4 ) page： e023719 2022.2

Language：English Publisher：Journal of the American Heart Association

BACKGROUND: Prognoses and long-term cardiac function of patients with fulminant myocarditis have not been fully elucidated. Therefore, we clarified the prognoses and long-term cardiac function according to required percutaneous mechanical circulatory support and histological findings among patients with fulminant myocarditis. METHODS AND RESULTS: We conducted a multicenter retrospective medical record review of 216 patients with fulminant my-ocarditis requiring percutaneous mechanical circulatory support. Sixty-one patients were treated with intra-aortic balloon pump or Impella alone, and 155 patients received veno-arterial extracorporeal membrane oxygenation and were treated with or without intra-aortic balloon pump or Impella. Histologically, 107 patients had lymphocytic myocarditis; 34, eosinophilic myocarditis; and 4, giant cell myocarditis. Freedom from composite end point (death, durable left ventricular assist device implantation, and heart transplantation) was 66% at 90 days, 62% at 1 year, and 57% at 6 years. Veno-arterial extracorporeal membrane oxygenation use was associated with poor prognosis in the multivariable analysis (hazard ratio [HR], 5.27; 95% CI, 1.60–17.36). The eosinophilic myocarditis subgroup showed better prognosis (HR, 0.28; 95% CI, 0.10– 0.80) compared with the lymphocytic myocarditis subgroup but not in the multivariable analysis. Ventricular tachycardia/ventricular fibrillation rhythm at admission, high C-reactive protein level, and no endomyocardial biopsy were also associated with poor prognosis. The left ventricular ejection fraction at 1 year was ≤50% in 16% of patients and was lower in patients with eosinophilic myocar-ditis (median: 57.9% [48.8– 65.0%]) than in those with lymphocytic myocarditis (65.0% [58.6– 68.7%]) (P=0.036). CONCLUSIONS: Patients with fulminant myocarditis who received veno-arterial extracorporeal membrane oxygenation had a poor prognosis. Long-term cardiac function was impaired in some patients, especially those with eosinophilic myocarditis.

DOI： 10.1161/JAHA.121.023719

Current Status of Outpatient Oral Antimicrobial Prescription and the Influence of Antimicrobial Stewardship for Inpatients: A Repeated Cross-Sectional Study at a Japanese Community Hospital

Tsuchimoto Daisuke, Morioka Hiroshi, Imaizumi Takahiro, Miyagawa Sawako, Yamamoto Masashi, Onishi Katsuhiro, Kuwabara Yukinori, Takada Kazuto, Watamoto Koichi

Biological and Pharmaceutical Bulletin Vol. 45 ( 9 ) page： 1340 - 1346 2022

Language：English Publisher：The Pharmaceutical Society of Japan

<p>This study aimed to clarify the details of outpatient oral antimicrobial use (AMU) at a Japanese community hospital and investigate the influence of the current inpatient-based antimicrobial stewardship (AS) on outpatients. A repeated cross-sectional study was conducted in Komaki City Hospital. Data on patients, physicians, and oral antibiotics were collected in October 2013, 2016, and 2019, and appropriateness of treatment and surgical antimicrobial prophylaxis (SAP) was evaluated. The percentage of patients receiving oral antibiotics increased significantly from 4.7% in 2013 (345/7338) to 5.9% in 2019 (365/6146), and the overall number of antimicrobial prescriptions per 1000 outpatients increased from 51.8 in 2013 to 68.0 in 2019. Prescriptions for third-generation cephalosporins per 1000 outpatients decreased (from 21.4 to 6.3), whereas the number of prescriptions for penicillin (from 3.8 to 15.3), fluoroquinolones (from 7.0 to 13.2), and co-trimoxazole (from 5.0 to 15.8) increased from 2013 to 2019. The appropriate AMU for overall infections significantly increased (from 68.4% in 2013 to 83.7% in 2019). The choice and duration of AMU significantly improved for SAP. However, even in 2019, only 29.3% of patients received antibiotics before surgery. The improved selection of antibiotics on outpatient prescription may be due to the influence of AS—which is focused on inpatients—while prescriptions for fluoroquinolones and prophylactics also increased. The challenges of antimicrobial administration after surgeries were also highlighted.</p>

DOI： 10.1248/bpb.b22-00309

Effect of body mass index on the association between alcohol consumption and the development of chronic kidney disease

Hashimoto, Y; Imaizumi, T; Kato, S; Yasuda, Y; Ishimoto, T; Kawashiri, H; Hori, A; Maruyama, S

SCIENTIFIC REPORTS Vol. 11 ( 1 ) page： 20440 2021.10

Language：English Publisher：Scientific Reports

The influence of body mass or metabolic capacity on the association between alcohol consumption and lower risks of developing chronic kidney disease (CKD) is not fully elucidated. We examined whether the body mass index (BMI) affects the association between drinking alcohol and CKD. We defined CKD as an estimated glomerular filtration rate decline < 60 mL/min/1.73 m2 and/or positive proteinuria (≥ 1+). Participants were 11,175 Japanese individuals aged 40–74 years without baseline CKD who underwent annual health checkups. Daily alcohol consumption at baseline was estimated using a questionnaire, and the participants were categorized as “infrequent (occasionally, rarely or never),” “light (< 20 g/day),” “moderate (20–39 g/day),” and “heavy (≥ 40 g/day).” Over a median 5-year observation period, 936 participants developed CKD. Compared with infrequent drinkers, light drinkers were associated with low CKD risks; adjusted hazard ratios (95% confidence intervals) were 0.81 (0.69–0.95). Stratified by BMI (kg/m2), moderate drinkers in the low (< 18.5), normal (18.5–24.9), and high (≥ 25.0) BMI groups had adjusted hazard ratios (95% confidence intervals) of 3.44 (1.60–7.42), 0.75 (0.58–0.98), and 0.63 (0.39–1.04), respectively. Taken together, the association between alcohol consumption and CKD incidence was not the same in all the individuals, and individual tolerance must be considered.

DOI： 10.1038/s41598-021-99222-y

Clinical impact of urinary CD11b and CD163 on the renal outcomes of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis

Yokoe, Y; Tsuboi, N; Imaizumi, T; Kitagawa, A; Karasawa, M; Ozeki, T; Endo, N; Sawa, Y; Kato, S; Katsuno, T; Maruyama, S; Yamagata, K; Usui, J; Nagata, M; Sada, KE; Sugiyama, H; Amano, K; Arimura, Y; Atsumi, T; Yuzawa, Y; Dobashi, H; Takasaki, Y; Harigai, M; Hasegawa, H; Makino, H; Matsuo, S

NEPHROLOGY DIALYSIS TRANSPLANTATION Vol. 36 ( 8 ) page： 1452 - 1463 2021.8

Language：English Publisher：Nephrology Dialysis Transplantation

Background: The detection of leukocyte-derived CD11b (α subunit of integrin Mac-1) and CD163 (scavenger receptor) in urine may reflect renal inflammation in antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN). The objective of this study was to evaluate the clinical significance of urinary CD11b (U-CD11b) and CD163 (U-CD163) in ANCA-GN. Methods: U-CD11b and U-CD163 were examined using enzyme-linked immunosorbent assay in ANCA-GN urine samples from our institutional cohort (n = 88) and a nationwide cohort (n = 138), and their association with renal histology was subsequently analyzed. Logistic regression analyses were performed on a nationwide ANCA cohort to determine the associations of the two urinary molecules with renal remission failure at 6 months or with yearly estimated glomerular filtration rate (eGFR) slope over a 24-month observation period. Results: U-CD11b and U-CD163 were significantly associated with cellular crescent formation and leukocyte accumulation in glomerular crescents. With regard to interstitial inflammation, both levels of U-CD11b and U-CD163 at diagnosis remarkably increased in ANCA-GN compared with the levels observed in nonglomerular kidney disorders including nephrosclerosis, immunoglobulin G4-related disease and tubulointerstitial nephritis; however, the presence of U-CD11b alone was significantly correlated with tubulointerstitial leukocyte infiltrates. Although neither U-CD11b nor U-CD163 at diagnosis was associated with remission failure at 6 months, multivariate analysis demonstrated that the baseline U-CD11b levels were significantly associated with the increase in eGFR following immunosuppressive therapy. Conclusions: Although both U-CD11b and U-CD163 reflect renal leukocyte accumulation, U-CD11b at diagnosis provides additional clinical value by predicting the recovery rate after the treatment of ANCA-GN.

DOI： 10.1093/ndt/gfaa097

Comparison between the effects of normal saline with and without heparin for the prevention and management of arterial catheter occlusion: a triple-blinded randomized trial

Tamura, T; Kobayashi, E; Kawaguchi, M; Matsuoka, Y; Fujii, A; Ando, M; Kubo, Y; Imaizumi, T; Miyagawa, Y; Inagaki, T; Nishiwaki, K

JOURNAL OF ANESTHESIA Vol. 35 ( 4 ) page： 536 - 542 2021.8

Language：English Publisher：Journal of Anesthesia

Purpose: We aimed to compare the effects of saline with and without heparin on the catheter-occlusion rate and coagulation-related blood test results for the management of arterial catheters among patients admitted to a short-term intensive care unit postoperatively. Methods: This prospective, triple-blinded, randomized controlled study recruited patients aged 20–90 years scheduled to undergo radial arterial catheter insertion and postoperative intensive care unit admission between February and August 2019. Patients were randomly allocated to two groups (1:1 ratio) depending on the use of heparin: study (normal saline with heparin, 3000 units to 500 ml of normal saline) and control (normal saline without heparin) groups with arterial catheters. The allocated management method was employed immediately after intensive care unit admission. Occlusion assessment (every 12 h), arterial blood gas tests (every 6 h), and blood sample collection (every 24 h) were performed. The occlusion of arterial catheter was assessed using occlusion rate, and blood test results were assessed using a linear mixed model. Results: There were 147 patients in the arterial catheter groups. There were no significant differences in occlusion rates and changes in platelet counts and activated partial thromboplastin time between the groups with arterial (p = 0.98, 0.16, and 0.32, respectively) catheters during the first 6 days after intensive care unit admission. Conclusion: Normal saline with and without heparin showed similar efficiency for both the prevention of occlusion and the results of coagulation.

DOI： 10.1007/s00540-021-02949-1

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