Language：English   Publisher：Scientific Reports  

We present a single-center retrospective analysis of 228 Japanese patients with peritoneal dialysis, in which we examined whether reduced left ventricular ejection fraction (LVEF) is a risk factor for peritonitis development. Time-dependent multivariable-adjusted Cox proportional hazards models revealed that reduced LVEF (LVEF < 50% vs. preserved LVEF ≥ 50%, hazard ratio (HR) 2.10; 95% confidence interval (CI) 1.16–3.82) was associated with peritonitis. Qualitatively, similar associations with reduced LVEF (< 50%) were observed for enteric peritonitis (adjusted HR 7.68; 95% CI 2.51–23.5) but not for non-enteric peritonitis (adjusted HR 1.15; 95% CI 0.54–2.44). Reduced LVEF is associated with a significantly higher risk of subsequent peritonitis, particularly enteric peritonitis. These results indicate that patients with reduced LVEF may be at risk of enteric peritonitis from bowel sources caused by intestinal involvement due to cardiac dysfunction.

DOI： 10.1038/s41598-023-49744-4

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Language：English   Publisher：Journal of the American Medical Directors Association  

Objectives: Limited data exist regarding association between physical performance and in-hospital falls. This study was performed to investigate the association between physical performance and in-hospital falls in a high-risk population. Design: Retrospective cohort study. Setting and Participants: The study population consisted of 1200 consecutive patients with a median age of 74 years (50.8% men) admitted to a ward with high incidence rates of falls, primarily in the departments of geriatrics and neurology, in a university hospital between January 2019 and December 2021. Methods: Short Physical Performance Battery (SPPB) was measured after treatment in the acute phase. As the primary end point of the study, the incidence of in-hospital falls was examined prospectively based on data from mandatory standardized incident report forms and electronic patient records. Results: SPPB assessment was performed at a median of 3 days after admission, and the study population had a median SPPB score of 3 points. Falls occurred in 101 patients (8.4%) over a median hospital stay of 15 days. SPPB score showed a significant inverse association with the incidence of in-hospital falls after adjusting for possible confounders (adjusted odds ratio for each 1-point decrease in SPPB: 1.19, 95% CI 1.10-1.28; P < .001), and an SPPB score ≤6 was significantly associated with increased risk of in-hospital falls. Inclusion of SPPB with previously identified risk factors significantly increased the area under the curve for in-hospital falls (0.683 vs. 0.740, P = .003). Conclusion and Implications: This study demonstrated an inverse association of SPPB score with risk of in-hospital falls in a high-risk population and showed that SPPB assessment is useful for accurate risk stratification in a hospital setting.

DOI： 10.1016/j.jamda.2023.07.020

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Language：English   Publisher：Nephrology Dialysis Transplantation  

Background: The optimal range of serum iron markers and usefulness of iron supplementation are uncertain in patients with pre-dialysis chronic kidney disease (CKD). We investigated the association between serum iron indices and risk of cardiovascular disease (CVD) events and the effectiveness of iron supplementation using Chronic Kidney Disease Japan Cohort data. Methods: We included 1416 patients ages 20-75 years with pre-dialysis CKD. The tested exposures were serum transferrin saturation and serum ferritin levels and the outcome measures were any cardiovascular event. Fine-Gray subdistribution hazard models were used to examine the association between serum iron indices and time to events. The multivariable fractional polynomial interaction approach was used to evaluate whether serum iron indices were effect modifiers of the association between iron supplementation and cardiovascular events. Results: The overall incidence rate of CVD events for a median of 4.12 years was 26.7 events/1000 person-years. Patients with serum transferrin saturation <20% demonstrated an increased risk of CVD [subdistribution hazard ratio (HR) 2.13] and congestive heart failure (subdistribution HR 2.42). The magnitude of reduction in CVD risk with iron supplementation was greater in patients with lower transferrin saturations (P =. 042). Conclusions: Maintaining transferrin saturation >20% and adequate iron supplementation may effectively reduce the risk of CVD events in patients with pre-dialysis CKD.

DOI： 10.1093/ndt/gfad096

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Language：English   Publisher：Journal of Infection and Chemotherapy  

Introduction: Cefmetazole (CMZ), an antibiotic with limited international distribution, is recommended by the Tokyo Guidelines 2018 (TG18) for non-severe cases of acute cholangitis (AC). However, the risk factors for CMZ-non-susceptible (CMZ-NS) bacteremia in AC remain unclear. Here, we aimed to investigate the risk factors for CMZ-NS bacteremia and evaluate mortality in patients with AC. Methods: This single-center, retrospective, observational study included all patients diagnosed with definite bacteremic AC, based on TG18, from April 2019 to March 2023. Risk factors for CMZ-NS bacteremia were analyzed by univariate, and age- and sex-adjusted, logistic regression analyses. Mortality was compared by cause of obstruction, CMZ-susceptible/CMZ-NS bacteremia, and initial treatment. Results: In total, 165 patients were enrolled. CMZ-NS bacteremia was diagnosed in 46 (27.9 %) patients. Histories of diabetes mellitus, hepato-biliary-pancreatic cancer, malignant biliary obstruction, and endoscopic sphincterotomy were identified as significant factors associated with the risk of CMZ-NS bacteremia. Thirteen patients died within 30 days of hospital admission. The mortality of patients with AC and malignant biliary obstruction was statistically higher than that of patients with bile duct stones. No patients with AC and bile duct stones died in the group with CMZ-NS bacteremia and inappropriate initial antibiotics. Conclusions: In AC, a history of diabetes mellitus, hepato-biliary-pancreatic cancer, malignant biliary obstruction, and endoscopic sphincterotomy are associated with an increased risk of CMZ-NS bacteremia. Therefore, the choice of empiric therapy for AC should be based on the etiology and patient background, rather than on the severity.

DOI： 10.1016/j.jiac.2023.11.015

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Language：English  

DOI： 10.1210/clinem/dgad660

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Publisher：日本メディカルセンター  

DOI： 10.19020/cd.0000002767

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Language：English   Publisher：Annals of Surgery  

Objective: To determine the goal of intraoperative blood loss in hepatectomy for perihilar cholangiocarcinoma. Background: Although massive bleeding can negatively affect the postoperative course, the target value of intraoperative bleeding to reduce its adverse impact is unknown. Methods: Patients who underwent major hepatectomy for perihilar cholangiocarcinoma between 2010 and 2019 were included. Intraoperative blood loss was adjusted for body weight [adjusted blood loss (aBL)], and the overall postoperative complications were evaluated by the comprehensive complication index (CCI). The impact of aBL on CCI was assessed by the restricted cubic spline regression. Results: A total of 425 patients were included. The median aBL was 17.8 (interquartile range, 11.8-26.3) mL/kg, and the CCI was 40.6 (33.7-49.5). Sixty-three (14.8%) patients had an aBL<10 mL/kg, nearly half (45.4%) of the patients were in the range of 10 ≤aBL<20 mL/kg, and 37 (8.7%) patients had an aBL >40 mL/kg. The spline regression analysis showed a nonlinear incremental association between aBL and CCI; CCI remained flat with an aBL under 10 mL/kg; increased significantly with an aBL ranging from 10 to 20 mL/kg; grew gradually with an aBL over 20 mL/kg. These inflection points of 10 and 20 mL/kg were almost consistent with the cutoff values identified by the recursive partitioning technique. After adjusting for other risk factors for the postoperative course, the spline regression identified a similar model. Conclusions: aBL had a nonlinear aggravating effect on CCI after hepatectomy for perihilar cholangiocarcinoma. The primary goal of aBL should be <10 mL/kg to minimize CCI.

DOI： 10.1097/SLA.0000000000005869

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Language：English   Publisher：Journal of Nephrology  

Background: The Japan Renal Biopsy Registry (J-RBR), a nationwide, web-based, registry system, started in 2007. This study aimed to summarise the epidemiology of biopsy-diagnosed kidney disease in Japan over 10 years. Methods: We analysed the J-RBR database, from 2007 to 2017. Patients’ clinical data collected at the time of biopsy and histopathological diagnoses were used for epidemiological and clinicopathologic analyses. Results: The predominant renal biopsy diagnoses were immunoglobulin A nephropathy (39.2%), lupus nephritis (6.5%) and minimal change disease (6.0%) in younger adults (19–64 years), and membranous nephropathy (17.4%), antineutrophil cytoplasmic antibody-associated vasculitis or anti-glomerular basement membrane glomerulonephritis (13.0%), and immunoglobulin A nephropathy (12.5%) in older adults (≥ 65 years). The percentages of patients diagnosed with membranoproliferative glomerulonephritis and immunoglobulin A nephropathy decreased, whereas those with immunoglobulin A vasculitis and diabetic nephropathy increased over the decade. In paediatric patients (< 19 years), immunoglobulin A nephropathy (36.1%), minimal change disease (17.6%), and immunoglobulin A vasculitis (8.6%) were the predominant diagnoses. The percentage of patients diagnosed with immunoglobulin A vasculitis increased over the decade. Based on the sex distribution, minimal change disease and membranous nephropathy were predominant in men aged < 20 and > 40 years, respectively, whereas immunoglobulin A vasculitis and antineutrophil cytoplasmic antibody-associated vasculitis or anti-glomerular basement membrane glomerulonephritis were predominant in women in their 20s and 30s and aged < 50 years, respectively. Immunoglobulin A nephropathy was predominant in men at most ages and in women in their 20s to 40s. Conclusions: This study describes the distribution and changes in kidney biopsy diagnoses over 10 years in Japan and paves the way for future research on kidney diseases in adults and children. Graphical abstract: [Figure not available: see fulltext.].

DOI： 10.1007/s40620-023-01687-9

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DOI： 10.3324/haematol.2023.283636

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Language：English   Publisher：Kidney International Reports  

Introduction: Despite recognized geographic and sex-based differences in hemoglobin in the general population, these factors are typically ignored in patients with chronic kidney disease (CKD) in whom a single therapeutic range for hemoglobin is recommended. We sought to compare the distribution of hemoglobin across international nondialysis CKD populations and evaluate predictors of hemoglobin. Methods: In this cross-sectional study, hemoglobin distribution was evaluated in each cohort overall and stratified by sex and estimated glomerular filtration rate (eGFR). Relationships between candidate predictors and hemoglobin were assessed from linear regression models in each cohort. Estimates were subsequently pooled in a random effects model. Results: A total of 58,613 participants from 21 adult cohorts (median eGFR range of 17–49 ml/min) and 3 pediatric cohorts (median eGFR range of 26–45 ml/min) were included with broad geographic representation. Hemoglobin values varied substantially among the cohorts, overall and within eGFR categories, with particularly low mean hemoglobin observed in women from Asian and African cohorts. Across the eGFR range, women had a lower hemoglobin compared to men, even at an eGFR of 15 ml/min (mean difference 5.3 g/l, 95% confidence interval [CI] 3.7–6.9). Lower eGFR, female sex, older age, lower body mass index, and diabetic kidney disease were all independent predictors of a lower hemoglobin value; however, this only explained a minority of variance (R2 7%–44% across cohorts). Conclusion: There are substantial regional differences in hemoglobin distribution among individuals with CKD, and the majority of variance is unexplained by demographics, eGFR, or comorbidities. These findings call for a renewed interest in improving our understanding of hemoglobin determinants in specific CKD populations.

DOI： 10.1016/j.ekir.2023.07.032

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Language：English   Publisher：Modern Rheumatology  

Objectives: Patients with rheumatoid arthritis (RA) usually switch to a second biological disease-modifying antirheumatic drugs (bDMARDs) when the first has proven to be ineffective, although some may discontinue bDMARDs treatment altogether. We investigated the total rate of bDMARDs retention and the risk of bDMARDs discontinuation in patients with RA. Methods: The study included 564 patients with RA who started bDMARDs treatment before 2008 (<65 years old, n = 413; ≥65, n = 151). The primary outcome was the incidence of bDMARDs discontinuation due to adverse events (AEs). Risk factors were examined using Fine and Gray regression models. Results: Among 564 patients, 74 had discontinued bDMARDs treatment due to AEs. Male sex and Steinbrocker class 3-4 were more frequent, while rheumatoid factor and concomitant methotrexate treatment were less frequent, in those aged ≥65 years than in those aged <65 years, respectively. The subdistribution hazard ratio for discontinuation was significantly higher in the ≥65 group than in the <65 years group (hazard ratio = 3.53, 95% confidence interval = 2.07-6.03). Lack of concomitant treatment with MTX was risk factor for discontinuation in patients ≥65 years. Advanced Steinbrocker class was a risk factor in patients <65 years. Conclusions: Older patients are at higher risk of discontinuing bDMARDs treatment due to AEs than younger patients.

DOI： 10.1093/mr/roac090

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Language：English   Publisher：International Journal of Cancer  

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m2, the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m2 were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m2 were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m2 revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m2, with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.

DOI： 10.1002/ijc.34554

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Language：English   Publisher：Clinical Neuroradiology  

Purpose: Artificial intelligence (AI)-based three-dimensional angiography (3D-A) was reported to demonstrate visualization of cerebral vasculature equivalent to that of three-dimensional digital subtraction angiography (3D-DSA). However, the applicability and efficacy of the AI-based 3D‑A algorithm have not yet been investigated for 3D-DSA micro imaging. In this study, we evaluated the usefulness of the AI-based 3D‑A in 3D-DSA micro imaging. Materials and Methods: The 3D-DSA micro datasets of 20 consecutive patients with cerebral aneurysm (CA) were reconstructed with 3D-DSA and 3D‑A. Three reviewers compared 3D-DSA and 3D‑A in terms of qualitative parameters (degrees of visualization of CA and the anterior choroidal artery [AChA]) and quantitative parameters (aneurysm diameter, neck diameter, parent vessel diameter, and visible length of AChA). Results: Qualitative evaluation of diagnostic potential revealed that visualization of CA and the proximal to middle parts of the AChA with 3D‑A was equal to that with conventional 3D-DSA; in contrast, visualization of the distal part of the AChA was lower with 3D‑A than with 3D-DSA. Further, regarding quantitative evaluation, the aneurysm diameter, neck diameter, and parent vessel diameter were comparable between 3D‑A and 3D-DSA; in contrast, the visible length of the AChA was lower with 3D‑A than with 3D-DSA. Conclusions: The AI-based 3D‑A technique is feasible and evaluable visualization of cerebral vasculature with respect to quantitative and qualitative parameters in 3D-DSA micro imaging. However, the 3D‑A technique offers lower visualization of such as the distal portion of the AChA than 3D-DSA.

DOI： 10.1007/s00062-023-01325-8

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Language：English   Publisher：American Heart Journal  

Background: We examined the relationship between annual case volume at each hospital and outcome in cardiogenic shock (CS) patients receiving mechanical circulatory support (MCS) devices. Methods: This cross-sectional study used the Japanese nationwide database to identify patients receiving short-term MCS for CS between April 2012 and March 2020. Of 65,837 patients, 3 subcohorts were created; the intra-aortic balloon pump (IABP) alone (n = 48,643), the extracorporeal membrane oxygenation (ECMO) (n = 16,871), and the Impella cohorts (n = 696). Results: The median annual case volume was 13.5 (7.4-22.1) in the IABP alone cohort, 6.4 (3.4-11.0) in the ECMO cohort, and 7.5 (4.0-10.7) in the Impella cohort. The highest quintile for the volume of cases in the IABP alone and ECMO had the lowest in-hospital mortality (IABP alone, 25.1% in quintile 1 vs 15.2% in quintile 5; ECMO, 73.7% in quintile 1 in 67.4% in quintile 5). Adjusted ORs for in-hospital mortality decreased as case volume increased (IABP alone, 0.63 [0.58-0.68] in quintile 5; ECMO, 0.73 [0.65-0.82] in quintile 5, with the lowest quintile as reference) but did not decrease significantly in the Impella (0.90 [0.58-1.39] in tertile 3, with the lowest tertile as reference). In the continuous models with the case volume as a continuous variable, adjusted ORs for in-hospital mortality decreased to 28 IABP cases/year and 12 ECMO cases/year. They did not decrease or became almost flat above that. Conclusions: Higher volumes of IABP and ECMO are associated with a lower mortality. There is an upper limit to the decline. Centralizing patients with refractory CS in a particular hospital might improve patient outcomes in each region.

DOI： 10.1016/j.ahj.2023.03.017

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Language：English   Publisher：European Heart Journal Cardiovascular Imaging  

Aims: Aortic valve calcification in aortic sclerosis, a precursor of aortic stenosis (AS), is not always present in all three leaflets; how calcification develops in each leaflet is unknown. We aimed to investigate the natural history of calcification development in each aortic valve leaflet and the prognostic value of the number of calcified leaflets. Methods and results: In a retrospective multicentre cohort study of patients undergoing haemodialysis without AS, we observed calcification development in each aortic valve leaflet using echocardiography. We investigated the association between the number of calcified leaflets and AS development and mortality using time-to-event analysis. Among the 1507 patients (mean age, 66 years; 66% male) included in the longitudinal echocardiography analysis, 709 (47%) had aortic sclerosis at baseline: one-leaflet calcified, 370 (52%); two-leaflet calcified, 215 (30%); and three-leaflet calcified, 124 (17%). The median time for one calcified leaflet increase was 3-4 years, and 251 (17%) patients developed AS during a median 3.2-year follow-up. The increased number of calcified aortic valve leaflets was associated with developing AS; compared with that of one-leaflet calcified, the adjusted hazard ratios (aHRs) [95% confidence intervals (CIs)] of two- and three-leaflet calcified were 2.12 (1.49-3.00) and 4.43 (3.01-6.52), respectively; the aHR (95% CI) per one calcified leaflet increase was 2.24 (1.96-2.55). It was also associated with all-cause mortality; the aHR (95% CI) per one calcified leaflet increase was 1.18 (1.08-1.27). Conclusion: The number of calcified aortic valve leaflets strongly predicted AS development and even mortality in patients undergoing haemodialysis, suggesting the usefulness of assessing calcification for each valve leaflet separately using echocardiography.

DOI： 10.1093/ehjci/jead020

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Language：English   Publisher：Journal of General Internal Medicine  

Background: Physicians frequently experience patients as difficult. Our study explores whether more empathetic physicians experience fewer patient encounters as difficult. Objective: To investigate the association between physician empathy and difficult patient encounters (DPEs). Design: Cross-sectional study. Participants: Participants were 18 generalist physicians with 3–8 years of experience. The investigation was conducted from August–September 2018 and April–May 2019 at six healthcare facilities. Main Measures: Based on the Jefferson Scale of Empathy (JSE) scores, we classified physicians into low and high empathy groups. The physicians completed the Difficult Doctor-Patient Relationship Questionnaire-10 (DDPRQ-10) after each patient visit. Scores ≥ 31 on the DDPRQ-10 indicated DPEs. We implemented multilevel mixed-effects logistic regression models to examine the association between physicians’ empathy and DPE, adjusting for patient-level covariates (age, sex, history of mental disorders) and with physician-level clustering. Key Results: The median JSE score was 114 (range: 96–126), and physicians with JSE scores 96–113 and 114–126 were assigned to low and high empathy groups, respectively (n = 8 and 10 each); 240 and 344 patients were examined by physicians in the low and high empathy groups, respectively. Among low empathy physicians, 23% of encounters were considered difficulty, compared to 11% among high empathy groups (OR: 0.37; 95% CI = 0.19–0.72, p = 0.004). JSE scores and DDPRQ-10 scores were negatively correlated (r = −0.22, p < 0.01). Conclusion: Empathetic physicians were less likely to experience encounters as difficult. Empathy appears to be an important component of physician perception of encounter difficulty.

DOI： 10.1007/s11606-022-07936-0

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Language：English   Publisher：Plant Communications  

The timing of flowering affects the success of sexual reproduction. This developmental event also determines crop yield, biomass, and longevity. Therefore, this mechanism has been targeted for improvement along with crop domestication. The underlying mechanisms of flowering are highly conserved in angiosperms. Central to these mechanisms is how environmental and endogenous conditions control transcriptional regulation of the FLOWERING LOCUS T (FT) gene, which initiates floral development under long-day conditions in Arabidopsis. Since the identification of FT as florigen, efforts have been made to understand the regulatory mechanisms of FT expression. Although many transcriptional regulators have been shown to directly influence FT, the question of how they coordinately control the spatiotemporal expression patterns of FT still requires further investigation. Among FT regulators, CONSTANS (CO) is the primary one whose protein stability is tightly controlled by phosphorylation and ubiquitination/proteasome-mediated mechanisms. In addition, various CO interaction partners, some of them previously identified as FT transcriptional regulators, positively or negatively modulate CO protein activity. The FT promoter possesses several transcriptional regulatory “blocks,” highly conserved regions among Brassicaceae plants. Different transcription factors bind to specific blocks and affect FT expression, often causing topological changes in FT chromatin structure, such as the formation of DNA loops. We discuss the current understanding of the regulation of FT expression mainly in Arabidopsis and propose future directions related to this topic.

DOI： 10.1016/j.xplc.2023.100552

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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CiNii Research

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

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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

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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

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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

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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

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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

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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

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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

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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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Language：English   Publisher：Atherosclerosis  

Background and aims: Mild-to-moderate aortic stenosis (AS) and aortic sclerosis, a precursor of AS, are associated with mortality in the general population; however, their association in patients undergoing hemodialysis with higher morbidity of AS is unknown. Thus, we investigated the mortality of aortic sclerosis and mild-to-moderate AS in patients undergoing hemodialysis. Methods: This was a retrospective multicenter cohort study of consecutive patients undergoing hemodialysis at nine dialysis facilities who underwent screening echocardiography between January 2008 and December 2019. We investigated the mortality of patients with aortic sclerosis or mild-to-moderate AS using multivariable Cox proportional hazards regression. Results: Among 1,878 patients undergoing hemodialysis, those with normal aortic valves, aortic sclerosis, mild AS, moderate AS, severe AS, and prosthetic aortic valves were 844 (45%), 793 (42%), 161 (8.6%), 38 (2.0%), 11 (0.6%), and 31 (1.7%), respectively. After excluding patients with severe AS and prosthetic aortic valves, we performed comparative analysis on 1,836 patients (mean age, 67 years; 66% male). In a median follow-up of 3.6 years, crude death rates (per 100 person-years) were 5.2, 10.6, and 13.0 in patients with normal aortic valves, aortic sclerosis, and mild-to-moderate AS, respectively. Compared with normal aortic valves, both aortic sclerosis and mild-to-moderate AS were associated with all-cause and cardiovascular death: adjusted hazard ratios (95% confidence intervals) were 1.36 (1.13–1.65) and 1.36 (1.02–1.80) for all-cause death; and 1.52 (1.06–2.17) and 1.74 (1.04–2.92) for cardiovascular death, respectively. Conclusions: Aortic sclerosis and mild-to-moderate AS were independent risk factors for all-cause and cardiovascular death in patients undergoing hemodialysis.

DOI： 10.1016/j.atherosclerosis.2021.06.910

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Language：English   Publisher：Journal of Diabetes Investigation  

Aims/Introduction: The relationship between renal function and urinary glucose is poorly understood in diabetes patients who are not using sodium–glucose cotransporter 2 inhibitors. This study aimed to investigate the association of urinary glucose excretion with renal function prognosis in such patients. Materials and Methods: This retrospective cohort study included 1,172 patients with type 1 or 2 diabetes mellitus. Patients were recruited and data were collected between 1 January 2007 and 31 December 2011; follow-up data were collected until 30 June 2015. The primary outcome was set as a 30% decline in estimated glomerular filtration rate relative to baseline. The relationship between this outcome and urinary glucose was investigated using Cox proportional hazards model. For analysis, patients were categorized into two groups: urinary glucose <5 g/day or ≥5 g/day. Interaction terms were analyzed. Results: Multivariate analysis showed that the prognosis of renal function was significantly better in patients with high urinary glucose (≥5 g/day; adjusted hazard ratio 0.58, 95% confidence interval 0.35–0.96; P = 0.034). Significant interactions were observed between high urinary glucose and male sex (hazard ratio 0.33, 95% confidence interval 0.14–0.74; P = 0.007), and between high urinary glucose and longer duration of diabetes (≥10 years; hazard ratio 0.25, 95% confidence interval 0.11–0.58; P = 0.001). Conclusions: The present study suggests that high urinary glucose is associated with prognosis in diabetes patients not taking sodium–glucose cotransporter 2 inhibitors. Measurement of 24-h urinary glucose excretion might have clinical utility for predicting renal prognosis.

DOI： 10.1111/jdi.13428

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Language：English   Publisher：Hypertension Research  

Cardiovascular disease (CVD) is a major complication in individuals with chronic kidney disease (CKD). In Japan, the incidence of CVD among persons with CKD is lower than that in the United States. Although various classes of antihypertensive agents are prescribed to prevent CVD, the proportion varies between the United States and Japan. Until now, few studies have compared clinical practices and CVD prevalence among patients with CKD in the United States vs. Japan. In this study, we performed a cross-sectional comparison of the prevalence of CVD and the prescription of β-blockers at study entry to the Chronic Kidney Disease Japan Cohort (CKD-JAC) Study and the Chronic Renal Insufficiency Cohort (CRIC) Study. The mean patient age was 58.2 and 60.3 years, the mean estimated glomerular filtration rate (eGFR) was 42.8 and 28.9 (mL/min/1.73 m2), and the median urinary albumin:creatinine ratio was 51.9 and 485.9 (mg/g) among 3939 participants in the CRIC Study and 2966 participants in the CKD-JAC Study, respectively. The prevalence of any CVD according to a self-report (CRIC Study) was 33%, while that according to a medical chart review (CKD-JAC Study) was 24%. These findings were consistent across eGFR levels. Prescriptions for β-blockers differed between the CRIC and CKD-JAC Studies (49% and 20%, respectively). The odds ratios for the association of any history of CVD and β-blocker prescription were 3.0 [2.6–3.5] in the CRIC Study and 2.0 [1.6–2.5] in the CKD-JAC Study (P < 0.001 for the interaction). In conclusion, the prevalence of CVD and treatment with β-blockers were higher in the CRIC Study across eGFR levels.

DOI： 10.1038/s41440-020-00608-8

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DOI： 10.1007/s00068-021-01718-9

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Language：English   Publisher：Leukemia  

DOI： 10.1038/s41375-021-01171-y

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Language：English   Publisher：Clinical and Experimental Nephrology  

Background: Hypernatremia is a major electrolyte disorder associated with death among critically ill patients. Glucocorticoid therapy may cause hypernatremia in refractory septic shock patients, but the association between glucocorticoid and intensive care unit (ICU)-acquired hypernatremia (IAH) remains unclear. The aim of this study was to clarify whether glucocorticoid administration was associated with IAH. Methods: This was a nested case–control study using data from an established cohort including 121 IAH cases identified from 1756 patients who were admitted to ICU in a tertiary care facility in Japan. We included patients who were admitted with a normal range of serum sodium concentrations (130–149 mEq/L) from January 1, 2013 to December 31, 2015 and remained in ICU for ≥ 2 days. Hypernatremia was defined as serum sodium concentration ≥ 150 mEq/L. Each case was matched to one control. Results: Multivariable conditional logistic regression revealed high-dose glucocorticoid {odds ratio (OR), 4.15 [95% confidence interval (CI) 1.29–13.4]}, acute kidney injury (AKI) [OR, 2.72 (95% CI 1.31–5.62)], and osmotic diuretics [OR, 3.44 (95% CI 1.41–8.39)] to be significantly associated with IAH. The contents and amounts of fluid infusion were not significantly associated with IAH. There were also significant duration–response effects between duration of glucocorticoid use and IAH; however, pulse glucocorticoid administration was not associated with IAH. Conclusion: In this nested case–control study, we demonstrated a significant association between IAH and high-dose glucocorticoid with significant duration–response effects. Serum sodium concentrations should be monitored carefully in critically ill patients administered prolonged high-dose glucocorticoid.

DOI： 10.1007/s10157-020-01967-9

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Language：English   Publisher：Scientific Reports  

Lupus nephritis (LN) is a life-threatening complication of systemic lupus erythematosus. The 2003 pathological classification of LN was revised in 2016; it quantitatively evaluates the interstitium in addition to the glomeruli. We performed a retrospective multi-centre cohort study and investigated the utility of the 2016 classification—including the activity index (AI), chronicity index (CI), and each pathological component to predict complete remission or renal function decline, defined as 1.5-fold increase in serum creatinine levels—and compare with that of the 2003 classification. Ninety-one consecutive adult patients with first-onset class III/IV LN who were newly prescribed any immunosuppressants were enrolled and followed up for a median of 51 months from January 2004. Cox regression analysis demonstrated the subclasses based on the 2003 classification, which mainly evaluate glomerular lesions, were not associated with clinical outcomes. After adjustments for estimated glomerular filtration rate and urinary protein levels, higher CI and higher interstitial fibrosis and lower hyaline deposit scores were associated with renal functional decline. Similarly, higher CI and interstitial inflammation scores were associated with failure to achieve complete remission. Therefore, the 2016 classification can predict the clinical outcomes more precisely than the 2003 classification.

DOI： 10.1038/s41598-020-78972-1

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Language：English   Publisher：The Japanese Society of Internal Medicine  

<p><b>Objective </b>Metabolic syndrome represents a unified condition of atherosclerotic diseases caused by abdominal obesity. The aims of this study were to examine the applicability of the prevalent fixed cut-off values of the abdominal circumference (AC) and body mass index (BMI) to age and gender groups and to identify suitable lifestyle modification factors. </p><p><b>Methods </b>We defined an outcome as having ≥ 2 risk components that are necessary to diagnose metabolic syndrome and examined the cross-sectional association of the AC and BMI with the outcome. We also assessed the effects of time-updated lifestyle information on metabolic traits using longitudinal data. </p><p><b>Patients </b> We enrolled 22,953 beneficiaries of a corporate health insurance scheme who underwent annual health examinations between January 2004 and December 2014. </p><p><b>Results </b>The AC [per 5-cm increase, odds ratio (OR) 1.17, 95% confidence interval (CI) 1.12-1.24] and BMI (OR 1.10, 95% CI 1.07-1.13) were significantly associated with the outcome, adjusted for age, gender, current smoking status, drinking habits, and other lifestyle information. The association between the outcome and AC was modified by gender (p for interaction = 0.033), and the association between the outcome and BMI was modified by age group (p for interaction = 0.049). In the longitudinal analysis, current smoking, drinking habits, and unhealthy eating habits were associated with an increased AC and BMI, whereas regular physical activity was associated with a decreased AC and BMI. </p><p><b>Conclusion </b>We showed that the association between the AC or BMI and metabolic syndrome was modified by gender or age group. Further studies will be needed to customize the national health screening and education programs. </p>

DOI： 10.2169/internalmedicine.5515-20

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Language：English   Publisher：Nagoya Journal of Medical Science  

Platelet Mapping can measure both the degree of platelet inhibition and fibrinogen activation, was not originally designed to measure fibrinogen concentration. Traditional laboratory fibrinogen concentration testing requires around 60 minutes; however, fibrinogen activation only takes 10 minutes, and is indicated as maximum amplitude of activator f. If Platelet Mapping can predict fibrinogen concentration during cardiopulmonary bypass, this could facilitate rapid hemostasis management. The aim of this study was to verify whether fibrinogen concentration could be predicted using Platelet Mapping results. Thus, a pilot study was conducted to evaluate this concept during cardiopulmonary bypass. This prospective, observational pilot study investigated 15- to 90-year-old patients who underwent cardiac or aortic surgery from August 2019 to September 2019. Twenty-one patients enrolled in this study, and 43 blood samples were obtained for both fibrinogen activation measurements using Platelet Mapping and traditional laboratory-based tests, respectively. Correlations between results were analyzed using linear regression and the receiver operating characteristic curve. Correlation by Pearson's correlation analysis indicates a significant relationship (correlation coefficient of r = 0.91), and a receiver operating characteristic curve indicated that sensitivity, specificity, and receiver operating characteristic area were 100% (95% confidence interval, 75.3-100%), 93.8% (79.2-99.2%), and 0.995 (0.984-1.00), respectively. Our results indicate a strong correlation between fibrinogen activation and serum fibrinogen concentration. The maximum amplitude of activator f can estimate low fibrinogen concentration faster than traditional methods; this method quickly provides important information for anesthesia and hemostatic management in cardiac surgery.

DOI： 10.18999/nagjms.82.4.623

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Language：English   Publisher：BMC Nephrology  

Background: Ankle-brachial index (ABI), the first-line diagnostic test for peripheral artery disease, can be falsely elevated when ankle arteries are incompressible, showing a J-shaped association with mortality. In this situation, toe-brachial index (TBI) is the recommended test. However, whether TBI provides additional prognostic information beyond ABI in patients on hemodialysis is unknown. Methods: In this retrospective cohort study of 247 Japanese prevalent hemodialysis patients (mean age 66.8 [SD 11.6] years), we evaluated mortality (116 deaths over a median follow-up of 5.2 years) related to quartiles of ABI and TBI, as well as three categories of low ABI (≤0.9), normal/high ABI (> 0.9) + low TBI (≤0.6), and normal/high ABI + normal TBI (> 0.6) using multivariable Cox models. Results: ABI showed a J-shaped association with mortality (adjusted hazard ratio 2.72 [95% CI, 1.52-4.88] in the lowest quartile and 1.59 [95% CI, 0.87-2.90] in the highest quartile vs. the second highest). Lower TBI showed a potentially dose-response association with mortality (e.g., adjusted hazard ratios 2.63 [95% CI, 1.36-5.12] and 2.89 [95% CI, 1.49-5.61] in the lowest two quartiles vs. the highest). When three categories by both ABI and TBI were analyzed, those with low ABI (≤0.9) experienced the highest risk followed by normal/high ABI (> 0.9) + low TBI (≤0.6). Among patients with normal/high ABI (> 0.9), the increased mortality risk in individuals with low TBI (≤0.6) compared to those with normal TBI (> 0.6) were significant (adjusted hazard ratio 1.84 [95% CI, 1.12-3.02]). Conclusions: Lower TBI was independently associated with mortality in patients on hemodialysis and has the potential to classify mortality risk in patients with normal/high ABI. Our results support the importance of evaluating TBI in addition to ABI in this clinical population.

DOI： 10.1186/s12882-020-01991-7

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Language：English   Publisher：PLoS ONE  

With the global problem of aging, it has become more difficult to improve the prognosis of older dialysis patients. Extended-hours hemodialysis offers longer treatment time compared to conventional hemodialysis regimen and provides favorable metabolic status, hemodynamic stability, and increased dietary intake. Despite prior studies reporting that in-center extended-hours hemodialysis can reduce the mortality rate, the treatment impact on elderly patients remains unclear. Therefore, we examined the association between extended-hours hemodialysis compared to conventional hemodialysis and all-cause mortality. Survival analyses using Cox proportional hazard model with multivariable adjustments and propensityscore based method were performed to compare mortality risk between 198 consecutive patients who started in-center extended-hours hemodialysis (Extended-HD) and 1407 consecutive patients who initiated conventional hemodialysis. The median age was 67.1 years in the Extended-HD group and 70.7 years in the conventional hemodialysis group. Extended-HD was associated with lower all-cause mortality in overall patients and the subgroup >70 years (adjusted hazard ratios of 0.60 [95% CI, 0.39-0.91] and 0.35 [95% CI, 0.18-0.69], respectively). There was a significant interaction between age >70 years and Extended-HD. In conclusion, extended-hours hemodialysis was associated with a lower mortality rate, especially in elderly patients. Copyright:

DOI： 10.1371/journal.pone.0235900

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Language：English   Publisher：Journal of Renal Nutrition  

Objective: Low body mass index (BMI) is a potential risk factor for mortality in patients on maintenance hemodialysis. This suggests the usefulness of BMI as a prognostic factor and implies the importance of nutritional status, inflammation, and oxidative stress, all of which affect BMI. We aimed to evaluate BMI changes over time and the mortality risk in patients undergoing a novel combination therapy consisting of an extended-hours hemodialysis protocol without dietary restrictions, which enabled sufficient nutrition. Design and Methods: This is a retrospective cohort study. Patients were divided into 2 groups based on BMI change (ΔBMI < 0, ΔBMI ≥ 0) between the 3rd and 12th month after transfer to the clinic. We studied the associations of BMI changes with all-cause mortality. Further subgroup analyses were performed using Cox models. We finally studied 187 patients who were receiving the combined therapy. The main outcome measure was all-cause mortality of the study group. Results: The median (interquartile range) follow-up time was 4.9 (3.0-8.6) years. Overall, 138 patients were in the ΔBMI ≥ 0 group. As per unadjusted and adjusted Cox models, maintained or increased BMI during this period was associated with hazard ratios of 0.45 (confidence interval 0.23-0.87, P <.05) and 0.35 (confidence interval 0.17-0.75, P <.01) for all-cause mortality, respectively. In the same group, maintained or increased BMI was found to be significantly associated with decreased mortality in female, older, and nondiabetic patients. The data indicated that diabetic status could have a modifying effect on the association between variation in BMI and mortality (P =.006). Conclusions: Extended-hours hemodialysis without dietary restrictions led to a beneficial effect of maintenance or increase in BMI, especially in females, patients aged ≥65 years, and those without diabetic nephropathy, which could lead to prolonged survival.

DOI： 10.1053/j.jrn.2019.06.002

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Language：English   Publisher：The Japanese Society of Internal Medicine  

<p><b>Objective </b>Exercise therapy is used for glycemic control in type 2 diabetes mellitus (T2DM). We evaluated the effects of intensive health guidance using the Internet of things (IoT) among Japanese company workers with early T2DM. </p><p><b>Methods </b>Fifty-three men (mean age: 54 years) with glycated hemoglobin (HbA1c) levels of >6.5% were enrolled in a 6-month exercise therapy program between August 2016 and January 2017. They used activity meters, scales, and sphygmomanometers connected to the Internet by Bluetooth. These devices automatically and continuously recorded daily information, and the participants simultaneously received health guidance from a public health nurse twice a month. </p><p><b>Results </b>The number of daily steps significantly increased, whereas the amount of physical activity increased but was not significant. The mean decrease (±SD) in HbA1c levels after 3 and 6 months was estimated to be -0.40% (±0.45, p<0.0001) and -0.19% (±0.55, p=0.033), respectively, by a linear mixed model that included baseline HbA1c levels and age as covariates. The program failed to improve the body mass index and blood pressure of the participants. The percentage of active stage (action and maintenance stage) in stage of health behavior significantly increased from 48% to 68% (p=0.011). </p><p><b>Conclusion </b>Intensive lifestyle intervention using a wearable monitoring system and remote health guidance improved diabetic control in middle-aged company workers. </p>

DOI： 10.2169/internalmedicine.3150-19

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Language：English   Publisher：BMC Medical Education  

Background: Frequent and repeated visits from patients with mental illness or free medical care recipients may elicit physicians' negative emotions and influence their clinical decision making. This study investigated the impact of the psychiatric or social background of such patients on physicians' decision making about whether to offer recommendations for further examinations and whether they expressed an appropriate disposition toward the patient. Methods: A randomized, controlled multi-centre study of residents in transitional, internal medicine, or emergency medicine was conducted in five hospitals. Upon randomization, participants were stratified by gender and postgraduate year, and they were allocated to scenario set 1 or 2. They answered questions pertaining to decision-making based on eight clinical vignettes. Half of the eight vignettes presented to scenario set 1 included additional patient information, such as that the patient had a past medical history of schizophrenia or that the patient was a recipient of free care who made frequent visits to the doctor (biased vignettes). The other half included no additional information (neutral vignettes). For scenario set 2, the four biased vignettes presented to scenario set 1 were neutralized, and the four neutral vignettes were rendered biased by providing additional information. After reading, participants answered decision-making questions regarding diagnostic examination, interventions, or patient disposition. The primary analysis was a repeated-measures ANOVA on the mean management accuracy score, with patient background information as a within-subject factor (no bias, free care recipients, or history of schizophrenia). Results: A total of 207 questionnaires were collected. Repeated-measures ANOVA showed that additional background information had influence on mean accuracy score (F(7, 206) = 13.84, p < 0.001 partial η2 = 0.063). Post hoc pairwise multiple comparison test, Sidak test, showed a significant difference between schizophrenia and no bias condition (p < 0.05). The ratings for patient likability were lower in the biased vignettes compared to the neutral vignettes, which was associated with the lower utilization of medical resources by the physicians. Conclusions: Additional background information on past medical history of schizophrenia increased physicians' mistakes in decision making. Patients' psychiatric backgrounds should not bias physicians' decision-making. Based on these findings, physicians are recommended to avoid being influenced by medically unrelated information.

DOI： 10.1186/s12909-019-1897-z

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Language：English   Publisher：PLoS ONE  

CD34+ cells maintain vascular homeostasis and predict cardiovascular outcomes. We previously evaluated the association of CD34+ cells with cardiovascular disease (CVD) events over 23 months, but long-term CVD outcomes in relation to levels of CD34+ cells in patients on maintenance hemodialysis are unclear. Herein, we analyzed the long-term predictive potential levels of CD34+ cells for CVD outcomes and all-cause mortality. Between March 2005 and May 2005, we enrolled 215 patients on maintenance hemodialysis at Nagoya Kyoritsu Hospital and followed them up to 12.8 years. According to the CD34+ cell counts, patients were classified into the lowest, medium, and highest tertiles. Levels of CD34+ cells were analyzed in association with four-point major adverse CV events (MACEs), CVD death, and all-cause mortality. In univariate analysis age, smoking habit, lower geriatric nutrition risk index, lower calcium × phosphate product, and lower intact parathyroid hormone were significantly associated with the lowest tertile. Whereas, in multivariate analysis, age and smoking habit were significantly associated with the lowest tertile. Among 139 (64.7%) patients who died during a mean follow-up period of 8.0 years, 39 (28.1%) patients died from CVD. Patients in the lowest tertile had a significantly lower survival rate than those in the medium and highest tertiles (p . 0.001). Using multivariable analyses, the lowest tertile was significantly associated with four-point MACEs (hazard ratio 1.80, p = 0.023) and CVD death (hazard ratio 2.50, p = 0.011). In conclusion, our long-term observational study revealed that a low level of CD34+ cells in the circulation predicts CVD outcomes among patients on maintenance hemodialysis.

DOI： 10.1371/journal.pone.0223390

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DOI： 10.1136/bmjopen-2018-028856

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Language：English   Publisher：PLoS ONE  

Predictive values of mesangial proliferation (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), and crescents (C) among 19 validation studies of the Oxford Classification of IgA nephropathy (IgAN) were discrepant, especially in Asian patients. These validation studies indicate that cutoffs of MESC score in the Oxford Classification may not be generalizable. Thus, we aimed to improve the clinical value of MESC scores by modifying the cutoff points. A total of 104 patients with IgAN were diagnosed from 2001 to 2012 vai renal biopsy and retrospectively evaluated at Nagoya University Hospital. The cutoff point for modified (M´E´S´C´) was determined using the receiver operating characteristic curve in association with renal outcome in the training cohort. Clinical values of the Oxford MESTC vs M´E´S´C´ cutoff points were analyzed using Kaplan-Meier and Cox regression in association with poor renal outcome in the validation and the entire cohort. Of 104 patients, 12.5% reached poor renal outcome over a median of 6.25 [4.16–9.61] years of follow-up. The modified cutoffs were defined as 40%, 10%, 20%, and 5% in the glomeruli for M´E´S´, and C´ respectively. In univariate analysis, E´, S ´, and T were significantly associated with poor renal outcome, whereas Oxford MESC, M´, and C´ in the training and validation cohort were not associated with poor renal outcome. Using multivariate analysis in the presence of estimated glomerular filtration rate (eGFR), only E´ was a significant predictive factor for poor renal outcome. The E´ with modified cutoff point of 10% significantly improved predictive value for poor renal outcome in IgAN. Therefore, the clinical value of modified cutoff points for M´E´S´C´ scores should be validated with various cohort studies in different regions.

DOI： 10.1371/journal.pone.0214414

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Language：English   Publisher：Nagoya Journal of Medical Science  

Recent epidemiological or immunopathological studies demonstrate the possible association between giant cell arteritis and infectious agents including Chlamydia pneumoniae. A 62-year-old Japanese man with type 1 diabetes mellitus developed biopsy-proven giant cell arteritis after acute upper respiratory infection. Serological examination indicated concurrent re-infection with C. pneumoniae. Clinical manifestations of the vasculitis subsided within a month without any immunosuppressive therapy, and no relapse was observed for the following 12 months. The natural history of this disease is unclear and spontaneous remission is rarely reported. The self-limiting nature of the infection could contribute to this phenomenon.

DOI： 10.18999/nagjms.81.1.151

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Publisher：Renal Replacement Therapy  

Background: Serum albumin is a marker of nourishment and inflammation. Although hypoalbuminemia in hemodialysis patients is reported as a risk factor for poor prognosis, few studies describe its effects on infectious diseases specifically. This study aimed to examine the relationship between the serum albumin level on admission and infection-related in-hospital death among hemodialysis patients. Methods: This was a multicenter retrospective observational study that was undertaken in Japan. We reviewed the medical records of 507 hemodialysis patients aged > 18 years, whose blood cultures were obtained based on suspicion of infectious disease, and who were managed at seven Japanese tertiary dialysis units from August 2011 to July 2013. The outcome measure was infection-related in-hospital death. Multivariate logistic regression models adjusted for age, sex, the dialysis vintage, diabetes mellitus, bacteremia, and log C-reactive protein levels were used for the statistical analysis. Results: Four hundred patients were analyzed and allocated to three groups based on their serum albumin levels: marked hypoalbuminemia (< 2.5 mg/dL), mild hypoalbuminemia (≤ 2.5-< 3.5 mg/dL), and normal albumin levels (≤ 3.5 mg/dL). The infection-related in-hospital death rates were 22.9% (n = 11), 12.5% (n = 25), and 4.6% (n = 7), respectively. The multivariate logistic regression models determined that a low serum albumin level was an independent risk factor for infection-related in-hospital death (odds ratio 0.35, 95% confidence interval 0.18-0.66). Conclusions: A low serum albumin level strongly predicts infection-related in-hospital death in hemodialysis patients hospitalized on suspicion of infection. Like those with bacteremia or diabetes mellitus, hemodialysis patients with hypoalbuminemia require careful management of their infections.

DOI： 10.1186/s41100-018-0173-8

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Language：English   Publisher：BMC Nephrology  

Background: Patients with late referral and positive history of volume overload may have a poor prognosis after initiating dialysis due to insufficient and/or inadequate management of complications of renal failure and the lack of better dialysis preparation. Little is known about the influence of the relationship between history of volume overload and late referral on prognosis. Methods: We analyzed 1475 patients who had initiated dialysis for the first time from October 2011 to September 2013. late referral was defined as referral to a nephrologist < 3 months before dialysis initiation. The major outcomes were all-cause death and deaths due to cardiovascular diseases (CVD). The impact of late referral and history of volume overload on all-cause mortality was assessed by Cox proportional hazards models. Results: Among 1475 patients, the mean patient age was 67.5 years. During the median follow-up of 2.2 years, 260 deaths occurred; 99 were due to CVD. Cox proportional hazards models demonstrated that late referral (adjusted hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.00-1.82) and history of volume overload (adjusted HR, 1.39; 95% CI, 1.06-1.81) were risk factors for all-cause mortality. Furthermore, late referral coexisting was associated with a history of volume overload increased mortality (adjusted HR, 2.10; 95% CI, 1.39-3.16 versus absence of late referral without history of volume overload) after adjusting for age, sex, diabetes, atherosclerotic disease, and laboratory values. Conclusions: Both late referral and history of volume overload were associated with increased risks of all-cause mortality. Trial registration: University Hospital Medical Information Network (UMIN000007096). Registered 18 January 2012, retrospectively registered. https://upload.umin.ac.jp/cgi-open-bin/ctr-e/ctr-view.cgi?recptno=R000008349.

DOI： 10.1186/s12882-018-0859-8

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Language：English   Publisher：Obesity Research and Clinical Practice  

Objective: Obesity, a risk factor for all-cause and cardiovascular mortality, is a major health concerns among middle-aged men. The aim of this study was to investigate a possible association of dietary habits and obesity related single nucleotide polymorphisms (SNPs) with obesity and metabolic abnormalities. Methods: We conducted a retrospective cohort study using annual health examination data of 5112 male workers, obtained between 2007 and 2011. Average dietary energy was estimated using electronically collected meal purchase data from cafeteria. We examined 8 SNPs related to obesity: GHRL rs696217, PPARG rs1175544, ADIPOQ rs2241766, ADIPOQ rs1501299, PPARD rs2016520, APOA5 rs662799, BRAP rs3782886, and ITGB2 rs235326. We also examined whether SNPs that were shown to associate with obesity affect other metabolic abnormalities such as blood pressure (BP), glucose, and lipid profile. Results: Average dietary energy significantly associated with increased abdominal circumference (AC) and body mass index (BMI). The odds ratios (ORs) of overweight and obesity also increased. The major allele of rs696217 significantly increased BMI and an increased OR with obesity, while the minor allele of rs3782886 was associated with significantly decreased AC and the decreased ORs with overweight and obesity. The minor allele of rs3782886 was also associated with significantly decreased systolic BP (SBP), triglyceride (TG), high-density lipoprotein (HDL), and fasting blood sugar (FBS), while rs696217 was not associated with other metabolic abnormalities. Conclusions: Average dietary energy in lunch, rs3782886, and rs696217 were associated with obesity, and rs3782886 was associated with other metabolic abnormalities.

DOI： 10.1016/j.orcp.2016.05.004

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Language：English   Publisher：Clinica Chimica Acta  

Introduction The protective effects of vascular endothelial growth factor (VEGF)-A165b on kidney tissue have been suggested in animal studies. However, the relevance of urinary and circulating VEGF-A165b levels in chronic kidney disease patients remains unclear. Therefore, the present study aimed to investigate the urinary and circulating VEGF-A165b levels in patients with chronic kidney disease. Methods This observational study enrolled a total of 92 Japanese patients with chronic kidney disease, who had undergone inulin renal clearance measurements for the accurate assessment of measured GFR. Urinary or circulating total VEGF-A and VEGF-A165b levels were measured using enzyme-linked immunosorbent assay. Results Urinary VEGF-A165b levels were significantly lower in G3a, G3b, and G4 + G5 category patients than in G1 + G2 category patients. Correlation analysis found that serum creatinine levels, serum cystatin C levels, eGFRcre, eGFRcys, and mGFR were weakly but significantly correlated with urinary VEGF-A165b levels. Additionally, circulating VEGF-A165b levels were significantly higher in G4 + G5 category patients than in G1 + G2 category patients. Conclusion A low urinary VEGF-A165b level reflects renal dysfunction in the chronic kidney disease stage, while a high circulating VEGF-A165b level cannot be attributed to decreased renal clearance.

DOI： 10.1016/j.cca.2017.10.014

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Language：English   Publisher：Clinical and Experimental Nephrology  

Background: The Oxford Classification is utilized globally, but has not been fully validated. In this study, we conducted a comparative analysis between the Oxford Classification and Japanese Histologic Classification (JHC) to predict renal outcome in Japanese patients with IgA nephropathy (IgAN). Methods: A retrospective cohort study including 86 adult IgAN patients was conducted. The Oxford Classification and the JHC were evaluated by 7 independent specialists. The JHC, MEST score in the Oxford Classification, and crescents were analyzed in association with renal outcome, defined as a 50% increase in serum creatinine. Results: In multivariate analysis without the JHC, only the T score was significantly associated with renal outcome. While, a significant association was revealed only in the JHC on multivariate analysis with JHC. Conclusions: The JHC and T score in the Oxford Classification were associated with renal outcome among Japanese patients with IgAN. Superiority of the JHC as a predictive index should be validated with larger study population and cohort studies in different ethnicities.

DOI： 10.1007/s10157-017-1393-x

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Language：English   Publisher：PLoS ONE  

Background: Proteinuria is a powerful prognostic factor for end-stage renal disease in IgA nephropathy (IgAN) patients. However, it is not known whether proteinuria exacerbations are related to seasonal changes. Methods: We retrospectively enrolled consecutive patients diagnosed with IgAN by kidney biopsy at our hospital between 2002 and 2014. Proteinuria remission was defined as urinary protein <0.3 g/gCr in two consecutive outpatient urinalyses and exacerbation as urinary protein 0.75 g/gCr. Four seasons were defined: spring (March–May), summer (June–August), autumn (September–November), and winter (December–February). We performed a multivariate analysis to identify factors associated with the second remission following a proteinuria exacerbation. Results: We analyzed 116 patients. Proteinuria remission and exacerbation occurred in 77, and 43 patients, respectively. The incidence of proteinuria exacerbation was significantly higher in autumn and winter than in spring and summer (p = 0.040). The cumulative second remission rate was significantly higher in patients with autumn and winter proteinuria exacerbation than in patients with spring and summer exacerbations (p = 0.0091). In multivariate analyses, exacerbation onset in autumn and winter (hazard ratio [HR], 3.51; 95% confidence interval [CI], 1.41–8.74) and intensive therapy (HR, 2.26; 95% CI, 1.05–4.88) were significantly associated with a second proteinuria remission. Conclusion: In IgAN patients in proteinuria remission, proteinuria exacerbation frequently occurred in autumn and winter. Exacerbations occurring in autumn and winter tended to remit early.

DOI： 10.1371/journal.pone.0187607

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Language：English   Publisher：PLoS ONE  

Background: Several single nucleotide polymorphisms (SNPs) have been implicated in the predisposition to chronic kidney disease (CKD). Atherosclerotic disease is deeply involved in the incidence of CKD; however, whether SNPs related to arteriosclerosis are involved in CKD remains unclear. This study aimed to identify SNPs associated with CKD and to examine whether risk allele accumulation is associated with CKD. Methods: We conducted a cross-sectional study using data of 4814 male workers to examine the association between estimated glomerular filtration rate (eGFR) and 59 candidate polymorphisms (17 CKD, 42 atherosclerotic diseases). We defined the genetic risk score (GRS) as the total number of risk alleles that showed a significant association in this analysis and examined the relationship with CKD (eGFR < 60 ml/min/1.73m2). Multivariate logistic regression, discrimination by area under the receiver operating characteristic curve, integrated discrimination improvement (IDI), and category-free net reclassification improvement (cNRI) were evaluated. Results: In total, 432 participants were categorized as having CKD. We found eight candidate SNPs with P value < 0.05 (CX3CR1 rs3732379, SHROOM3 rs17319721, MTP rs1800591, PIP5K1B rs4744712, APOA5 rs662799, BRAP rs3782886, SPATA5L1 rs2467853, and MCP1 rs1024611) in the multivariate linear regression adjusted for age, body mass index, systolic blood pressure, and fasting blood glucose. Among these eight SNPs, BRAP rs3782886 and SPATA5L1 rs2467853 were significantly associated with eGFR (false discovery rate < 0.05). GRS was significantly associated with CKD (odds ratio, 1.17; 95% confidence interval, 1.09–1.26). C-statisics improved from 0.775 to 0.780 but showed no statistical significance. However, adding GRS significantly improved IDI and cNRI (0.0057, P = 0.0028, and 0.212, P < 0.001, respectively). Conclusions: After adjustment for clinical factors, kidney function was associated with BRAP rs3782886 and SPATA5L1 rs2467853 and the GRS for CKD that we developed was associated CKD.

DOI： 10.1371/journal.pone.0185476

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Language：English   Publisher：BMJ Open  

Objectives: Hypernatraemia is one of the major electrolyte disorders associated with mortality among critically ill patients in intensive care units (ICUs). It is unclear whether this applies to patients with cerebrovascular diseases in whom high sodium concentrations may be allowed in order to prevent cerebral oedema. This study aimed to examine the association between ICU-acquired hypernatraemia and the prognosis of patients with cerebrovascular diseases. Design: A retrospective cohort study. Setting: The incidence of ICU-acquired hypernatraemia was assessed retrospectively in a single tertiary care facility in Japan. Participants: Adult patients (≥18 years old) whose length of stay in ICU was >2 days and those whose serum sodium concentrations were 130-149 mEq/L on admission to ICU were included. Outcome measures: 28-day in-hospital mortality risk was assessed by Cox regression analysis. Hypernatraemia was defined as serum sodium concentration ≥150 mEq/L. Using multivariate analysis, we examined whether ICU-acquired hypernatraemia and the main symptom present at ICU admission were associated with time to death among ICU patients. We also evaluated how the maximum and minimum sodium concentrations during ICU stay were associated with mortality, using restricted cubic splines. Results: Of 1756 patients, 121 developed ICU-acquired hypernatraemia. Multivariate Cox proportional hazard analysis revealed an association between ICU-acquired hypernatraemia and 28-day mortality (adjusted HR, 3.07 (95% CI 2.12 to 4.44)). The interaction between ICU-acquired hypernatraemia and cerebrovascular disease was significantly associated with 28-day mortality (HR, 3.03 (95% CI 1.29 to 7.15)). The restricted cubic splines analysis of maximum serum sodium concentration in ICU patients determined a threshold maximum of 147 mEq/L. There was no significant association between minimum sodium concentration and mortality. Conclusions: ICU-acquired hypernatraemia was associated with an increased mortality rate among critically ill patients with cerebrovascular diseases; the threshold maximum serum sodium concentration associated with mortality was 147 mEq/L.

DOI： 10.1136/bmjopen-2017-016248

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Language：English   Publisher：Therapeutic Apheresis and Dialysis  

Multiple studies have shown that Staphylococcus aureus bacteremia (SAB) has been a major cause of death in hemodialysis patients. We examined whether SAB is a risk for mortality among chronic hemodialysis patients in Japan where the standard vascular access is arteriovenous fistula (AVF). This was a multicenter, retrospective study of maintenance hemodialysis patients with bloodstream infection (BSI) from 2011 to 2013 at tertiary care centers in Japan. The endpoint was hospital mortality. Our cohort contained 32 SAB cases (14 MRSA and 18 MSSA) and 42 non-SAB cases. Hospital mortality was higher among SAB cases than non-SAB cases (46.9% vs. 23.8%, P = 0.038). In patients with BSI, SAB was significantly associated with hospital mortality after adjustment for potential confounders, including type of vascular access (OR 3.26). S. aureus was the leading cause of BSI and hospital mortality among this cohort. Therefore, initial empiric treatment should cover for S. aureus.

DOI： 10.1111/1744-9987.12534

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Language：English   Publisher：Clinical and Experimental Nephrology  

Background: Blood pressure is influenced by hereditary factors and dietary habits. The objective of this study was to examine the effect of dietary salt consumption and single-nucleotide polymorphisms (SNPs) on blood pressure (BP). Methods: This was a cross-sectional analysis of 2728 male participants who participated in a health examination in 2009. Average dietary salt consumption was estimated using electronically collected meal purchase data from cafeteria. A multivariate analysis, adjusting for clinically relevant factors, was conducted to examine whether the effect on BP of salt consumption, SNPs, and interaction between salt consumption and each SNP. This study examined the SNPs AGT rs699 (Met235Thr), ADD1 rs4961 (Gly460Trp), NPPA rs5063 (Val32Met), GPX1 rs1050450 (Pro198Leu), and AGTR1 rs5186 (A1166C) in relation to hypertension and salt sensitivity. Results: BP was not significantly associated with SNPs or salt consumption. The interaction between salt consumption and SNPs with systolic BP showed a significant association in NPPA rs5063 (Val32Met) (P = 0.023) and a marginal trend toward significance in rs4961 and rs1050450 (P = 0.060 and 0.067, respectively). Conclusion: The effect of salt consumption on BP differed by genotype. Dietary salt consumption and genetic variation can predict a high risk of hypertension.

DOI： 10.1007/s10157-016-1315-3

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Language：English   Publisher：PLoS ONE  

Background To our knowledge, no reliable clinical prediction rule (CPR) for identifying bacteremia in hemodialysis (HD) patients has been established. The aim of this study was to develop a CPR for bacteremia in maintenance HD patients visiting the outpatient department. Methods This multicenter cohort study involved consecutive maintenance HD patients who visited the outpatient clinic or emergency room of seven Japanese institutions between August 2011 and July 2013. The outcome measure was bacteremia diagnosed based on the results of blood cultures. The candidate predictors for bacteremia were extracted through a literature review. A CPR for bacteremia was developed using a coefficient-based multivariable logistic regression scoring method, and calibration was performed. The test performance was then assessed for the CPR. Results Of 507 patients eligible for the study, we analyzed the 293 with a complete dataset for candidate predictors. Of these 293 patients, 48 (16.4%) were diagnosed with bacteremia. At the conclusion of the deviation process, body temperature ô 38.3°t rate ô 125 /min, C-reactive protein ô 10 mg/dL, alkaline phosphatase >360 IU/L, and no prior antibiotics use within the past week were retained and scored. The CPR had a good fit for the model on calibration. The AUC of the CPR was 0.76, and for score CPR ô 2, the sensitivity and specificity were 89.6% and 51.4%, respectively. Conclusions We established a simple CPR for bacteremia in maintenance HD patients using routinely obtained clinical information in an outpatient setting. This model may facilitate more appropriate clinical decision making.

DOI： 10.1371/journal.pone.0169975

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Language：English   Publisher：The Japanese Society of Internal Medicine  

<p>A 26-year-old Japanese man without hypouricemia and with 3 previous episodes of seizures concurrent with acute kidney injury (AKI) was admitted due to an epileptic seizure, lower back pain and AKI. His creatinine kinase levels were slightly elevated. Patchy renal ischemia on contrast-enhanced computed tomography and persistent residual contrast medium was observed, consistent with acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise (ALPE). Diffusion-weighted imaging (DWI) demonstrated signal changes in the corresponding area. ALPE should be considered a cause of AKI following seizures. We recommend DWI as an alternative diagnostic modality. </p>

DOI： 10.2169/internalmedicine.56.8328

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