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This study aimed to clarify other diseases claimed simultaneously with acute upper respiratory infection (URI), antibiotic prescriptions, and examinations associated with infectious diseases in pediatric patients with acute URI insurance claims at otorhinolaryngology outpatient visits. Pediatric patients who visited an otolaryngology department between 2019 and 2021 and were definitively diagnosed with URI were selected using a large Japanese medical claims database. Patient backgrounds, antibiotic use, and examinations were descriptively evaluated. In total, 8010 patients were included in the analysis. The median number (interquartile range) of diseases claimed in the same month as acute URI was 4 (3-6). Only 519 (6.5 %) patients were claimed as acute URI alone. Regardless of the prescription of antibiotics, the most commonly redundantly claimed disease in these patients was allergic rhinitis, followed by acute bronchitis, acute sinusitis, and earwax impaction. The frequently prescribed antibiotics were third-generation cephalosporins, macrolides, and penicillins with extended-spectrum, including amoxicillin which was recommended by the Japanese manual; the proportion of patients with examinations was low (2.9-21.7 %). Among patients with acute URI, diagnoses requiring antibiotics were also claimed; therefore, when evaluating acute URI using the Japanese medical claims database, care must be taken in patient selection. Moreover, the implementation rate of examinations necessary for diagnosis was low, so there is an urgent need to develop an environment where examinations can be conducted in outpatient settings., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Proton pump inhibitor (PPI) use may be associated with renal dysfunction. Renal dysfunction in PPI users requires evaluation of development and progression risks simultaneously, using estimated glomerular filtration rate (eGFR) slope, which indicates changes in eGFR per year. To the best of our knowledge, no studies have evaluated eGFR slope in PPI users. This study investigated the association between PPI use and renal dysfunction using eGFR slope. A single-center cohort study was conducted using the health records data at Hamamatsu University Hospital in Japan. Participants were defined as first users of acid-suppressing drugs (PPIs or Histamine H 2 receptor antagonists (H 2 RAs)) from 2010 to 2021 and continuously prescribed for  ≥ 90 days. The H 2 RA group was used for the propensity-score matching (PSM) to the PPI group to minimize the effects of confounders. The eGFR slope was estimated using a linear mixed effects model. Participants were stratified by baseline eGFR and age, respectively, as subgroup analyses. A total of 4,649 acid-suppressing drug users met the inclusion criteria, including 950 taking H 2 RAs and 3,699 PPIs. After PSM, 911 patients were assigned to each group. The eGFR slopes of the PPI and H 2 RA users were -4.75 (95% CI: -6.29, -3.20) and -3.40 (-4.38, -2.42), respectively. The difference between the groups was not significant. Significant declines in eGFR were observed with PPIs with baseline eGFR ≥ 90 and age  < 65. PPI use for  ≥ 90 days may hasten eGFR decline compared to H 2 RA use, especially in patients with eGFR  ≥ 90 or age  < 65., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Information regarding the status of surgical antimicrobial prophylaxis (SAP) in Japanese hospitals is lacking. This study aimed to explore the status of SAP prescriptions for surgeries and adherence to Japanese SAP guidelines., Methods: From February to July 2020, a 1-day multicentre point prevalent survey was conducted at 27 hospitals in Aichi Prefecture, Japan. Patients prescribed SAP were included in this study. The appropriateness of the SAP was evaluated based on the guidelines for selection of antimicrobials and their duration. Surgery was defined as appropriate when all the items were appropriate., Results: A total of 728 patients (7.1 %; 728/10,199) received antimicrobials for SAP. Among them, 557 patients (76.5 %, 557/728) underwent the surgeries described in the guidelines. The overall appropriateness of all surgeries was 33.9 % (189/557). The appropriate selection of antimicrobial before/during and after surgery and their durations were 67.5 % (376/557), 67.5 % (376/557), and 43.3 % (241/557), respectively. The overall appropriateness ranged from 0 % (0/37, oral and maxillofacial surgery) to 58.7 % (88/150, orthopaedic surgery) and 27.7 % (36/130, community hospitals with 400-599 beds) to 47.2 % (17/36, specific hospitals). Cefazolin was the most prevalent antimicrobial prescribed before/during (55.5 %, 299/539), and after (45.1 %, 249/552) surgery. In total, 101 oral antimicrobials were prescribed postoperatively., Conclusions: SAP adherence by specific surgical fields and hospitals was shown in this study. Intensive intervention and repeated surveillance are necessary to improve SAP prescriptions in Japanese hospitals., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest relevant to this article., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

There is no clinical evidence of differences in drugs associated with long-term survival in patients with pulmonary arterial hypertension (PAH) due to the small population and lack of information on death in Japanese medical database systems. This study evaluated whether patient data from a spontaneous reporting database could be used for comparing the effects of pulmonary vasodilators on long-term survival in PAH patients. PAH patient data reported in the Japanese Adverse Drug Event Report (JADER) database from April 2004 to July 2022 were extracted. Kaplan-Meier curves were used to compare survival times. Adjusted hazard ratios (aHRs) for all-cause mortality were determined using Cox proportional hazards models. Of 1969 PAH patients reported in the JADER database, 1208 were included in the survival analyses. The patient demographics were similar to those of the PAH population reported in the Japan Pulmonary Hypertension Registry. Among drugs targeting the prostacyclin pathway, epoprostenol was most associated with long-term survival (aHR, 0.38; 95% confidence interval (CI), 0.23-0.64). The PAH patients treated with endothelin receptor antagonists had improved survival, especially among the macitentan users (aHR, 0.30; 95% CI, 0.22-0.42). Sildenafil was associated with a poor prognosis in the PAH patients (aHR, 1.56; 95% CI, 1.19-2.04). Although our results must be interpreted with caution due to several limitations inherent to spontaneous reporting databases, our approach using the JADER database for survival analysis may provide useful information in limited situations such as the treatment of rare diseases including PAH., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Limited research has evaluated the long-term outcomes of prospective audit and feedback (PAF) led by pharmacists. We assessed pharmacist-led PAF processes and outcome measures over 8 years., Methods: This study was conducted at a single public hospital in Japan. Between 2014 and 2021, pharmacists conducted weekday PAFs for hospitalized patients and annually evaluated the process and outcome measures. The endpoints included detection of drug-resistant bacteria, drug susceptibility rates, duration of antimicrobial therapy, and proportion of long-term administration., Results: Among inpatients, methicillin-resistant Staphylococcus aureus significantly decreased from 50.9% in 2014 to 32.8% in 2021 (P < .001). The susceptibility rate of Pseudomonas aeruginosa to meropenem significantly increased from 91.2% in 2014 to 94.4% in 2021 (P < .001) and levofloxacin increased from 84.9% in 2014 to 89.3% in 2021 (P < .001). Antimicrobial therapy duration did not differ significantly between 2014 and 2016, but decreased significantly from 2017 onwards (P < .001), except in 2018. The number of patients receiving intravenous antimicrobials for >10 days decreased significantly between 2014 and 2021 (P < .001)., Conclusions: Long-term continuous PAF interventions by pharmacists contribute to improving and maintaining process and outcome indicators and prevent the spread of drug-resistant bacteria., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Streptococcus mitis/oralis group isolates with reduced carbapenem susceptibility have been reported, but its isolation rate in Japan is unknown. We collected 356 clinical α-hemolytic streptococcal isolates and identified 142 of them as S. mitis/oralis using partial sodA sequencing. The rate of meropenem non-susceptibility was 17.6% (25/142). All 25 carbapenem-non-susceptible isolates harbored amino acid substitutions in/near the conserved motifs in PBP1A, PBP2B, and PBP2X. Carbapenem non-susceptibility is common among S. mitis/oralis group isolates in Japan., Competing Interests: The authors declare no conflict of interest.

Background and Aims: Few data exist regarding the gender differences in the relationship between triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and cardiometabolic risk leading to atherosclerotic cardiovascular disease (ASCVD). We investigated, by gender, the association between the TG/HDL-C ratio and metabolic syndrome (MetS) and its components in the Japanese, who are less obese than their Western counterparts., Methods and Results: A population consisting of 10,373 participants (average age, 47.6 ± 12.6 years, 60.9 % men) at the Health Planning Center of Nihon University Hospital between April 2019 and March 2020 was studied using a cross-sectional study method. The TG/HDL-C ratio and proportion of visceral obesity increased approximately parallelly with age in women; however, these parameters did not change proportionally with age in men. Accordingly, receiver operating characteristic analysis revealed the accuracy of the TG/HDL-C ratio as a predictor of visceral obesity based on the Japanese MetS criteria (women vs. men: area under the curve, 0.797 vs. 0.712, p < 0.0001; sensitivity, 82.4 % vs. 59.9 %; specificity, 61.1 % vs. 71.1 %; cutoff value, 1.075 vs. 1.933, respectively). Furthermore, a higher TG/HDL-C ratio in women reflected the status of MetS and its components compared with men in multi-logistic regression analysis., Conclusion: An increased TG/HDL-C ratio in women may be involved in MetS and its components compared to men. We may pay attention to visceral obesity and increased TG/HDL-C ratio to prevent ASCVD risk in women, even in the Japanese population, which generally contains a lower proportion of obesity than in Western populations., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: International consensus on cardiopulmonary resuscitation (CPR) and emergency cardiovascular care science and treatment recommendations (CoSTR) have reported updates on CPR maneuvers every 5 years since 2000. However, few national population-based studies have investigated the comprehensive effectiveness of those updates for out-of-hospital cardiac arrest due to shockable rhythms. The primary objective of the present study was to determine whether CPR based on CoSTR 2005 or 2010 was associated with improved outcomes in Japan, as compared with CPR based on Guidelines 2000., Methods and Results: From the All-Japan Utstein Registry between 2005 and 2015, we included 73 578 adults who had shockable out-of-hospital cardiac arrest witnessed by bystanders or emergency medical service responders. The study outcomes over an 11-year period were compared between 2005 of the Guidelines 2000 era, from 2006 to 2010 of the CoSTR 2005 era, and from 2011 to 2015 of the CoSTR 2010 era. In the bystander-witnessed group, the adjusted odds ratios for favorable neurological outcomes at 30 days after out-of-hospital cardiac arrest by enrollment year increased year by year (1.19 in 2006, and 3.01 in 2015). Similar results were seen in the emergency medical service responder-witnessed group and several subgroups., Conclusions: Compared with CPR maneuvers for shockable out-of-hospital cardiac arrest recommended in the Guidelines 2000, CPR maneuver updates in CoSTR 2005 and 2010 were associated with improved neurologically intact survival year by year in Japan. Increased public awareness and greater dissemination of basic life support may be responsible for the observed improvement in outcomes., Registration: URL: https://www.umin.ac.jp/ctr/; Unique identifier: 000009918.

High fish consumption may be associated with lower inflammation, suppressing atherosclerotic CVD (ASCVD). Long sleep duration, as well as short sleep, may contribute to inflammation, thus facilitating ASCVD. This study investigated the overall association between fish consumption, sleep duration and leucocytes count. We conducted a cross-sectional study between April 2019 and March 2020 with a cohort of 8947 apparently healthy participants with no history of ASCVD (average age, 46·9 ± 12·3 years and 59 % males). The average frequency of fish consumption and sleep duration were 2·13 ± 1·26 d/week and 6·0 ± 0·97 h/d. Multivariate linear regression analysis revealed that increased fish consumption was an independent determinant of sleep duration ( β = 0·084, P < 0·0001). Additionally, habitual aerobic exercise ( β = 0·059, P < 0·0001) or cigarette smoking ( β = −0·051, P < 0·0001) and homoeostasis model assessment-insulin resistance (HOMA-IR) ( β = −0·039, P = 0·01) were independent determinants of sleep duration. Furthermore, multivariate linear regression analysis identified fish consumption as an independent determinant of leucocytes count ( β = −0·091, P < 0·0001). However, a significant U-shaped curve was found between leucocytes count and sleep duration, with 6–7 h of sleep as the low value ( P = 0·015). Higher fish consumption may be associated with a lower leucocytes count in the presence of adequate sleep duration and healthy lifestyle behaviors. However, long sleep duration was also related to increased inflammation, even in populations with high fish consumption. Further studies are needed to clarify the causality between these factors.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been widely used for critically ill patients all over the world; however, comprehensive survey regarding the relationship between VA-ECMO duration and prognosis is limited. We conducted a survey of VA-ECMO patients in the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC), which was a health insurance claim database study among cardiovascular centers associated with the Japan Circulation Society, between April 2012 and March 2016. Out of 13,542 VA-ECMO patients, we analyzed 5766 cardiovascular patients treated with VA-ECMO. 68% patients used VA-ECMO only for 1 day and 93% had VA-ECMO terminated within 1 week. In multivariate analysis, the hazard ratio of 1-day support was significantly high at 1.72 (95% confidence intervals; 95% CI 1.53-1.95) (p < 0.001), while that of 2-day [0.60 (95% CI 0.49-0.73)], 3-day [0.75 (95% CI 0.60-0.94)], 4-day [0.43 (95% CI 0.31-0.60)] and 5-day support [0.62 (95% CI 0.44-0.86)] was significantly low. Comprehensive database analysis of JROAD-DPC revealed that cardiovascular patients who were supported with VA-ECMO for 2-5 days showed lower mortality. The optimal VA-ECMO support window should be investigated in further studies., (© 2022. Springer Japan KK, part of Springer Nature.)

Background: The Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system aggregates information related to antimicrobial resistance (AMR) measures in participating medical institutions nationwide and is intended to be used for promotion of AMR measures in participating facilities and their communities. This multicenter study aimed to determine the usefulness of the J-SIPHE system for evaluating the correlation between antibiotic use and antibiotic resistance in Hokkaido, Japan., Methods: Data on antibiotic use and detection rate of major resistant Gram-negative bacteria at 19 hospitals in 2020 were collected from the J-SIPHE system, and data correlations were analyzed using JMP Pro., Results: The detection rate of carbapenem-resistant Pseudomonas aeruginosa was significantly positively correlated with carbapenem use (Spearman's ρ = 0.551; P = .015). There were significant positive correlations between the detection rate of fluoroquinolone-resistant Escherichia coli and the use of piperacillin/tazobactam, carbapenems, and quinolones [ρ = 0.518 (P = .023), ρ = 0.76 (P < .001), and ρ = 0.502 (P = .029), respectively]., Conclusions: This is the first multicenter study to investigate the correlation between antibiotic use and antibiotic resistance using the J-SIPHE system. The results suggest that using this system may be beneficial for promoting AMR measures., (Copyright © 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: High fish consumption may be involved in lowering inflammation, resulting in the suppression of atherosclerotic cardiovascular disease (ASCVD) development. The monocyte/high-density lipoprotein cholesterol (HDL-C) ratio (MHR) is reported as a novel inflammatory marker of the development of atherosclerosis. We investigated the relationship between fish consumption, MHR, and lifestyle behaviors and explored the foundation of risk stratification of ASCVD using serum HDL-C, MHR, and fish consumption., Methods: We conducted a cross-sectional study among 6841 adults at the Health Planning Center of Nihon University Hospital between April 2019 and March 2020. We calculated the amount of fish consumption based on Japan's National Nutrition Survey results., Results: The median (interquartile range) fish consumption was 111.4 (67.2/169.2) g per week. As fish consumption increased, MHR decreased significantly (p < 0.0001). Multivariate linear regression analysis identified increased fish consumption as an independent negative determinant of a decreased MHR (β = -0.050, p < 0.0001). Additionally, healthier lifestyle behaviors (sleep duration and cigarette smoking habit) were also significantly associated with MHR (β = -0.025, p = 0.027 and β = 0.146, p < 0.0001, respectively). Furthermore, risk stratification of ASCVD could be developed by combining the HDL-C level and fish consumption with the MHR, indicating that even with similar HDL-C levels, higher MHR and lower fish consumption are associated with a higher risk of ASCVD. Multi-logistic regression analysis with the MHR quartile as an independent variable also showed that the increase in quartile was associated with the exacerbation of visceral obesity and glucose/lipid markers., Conclusions: A higher fish consumption may be associated with a lower MHR as well as healthier lifestyle behaviors. Moreover, we proposed the concept of risk stratification through relationships with MHR, HDL-C, and fish consumption to reduce ASCVD risk. Further studies are required to dissect the causal relationships between these results., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest to declare., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Surgical antimicrobial prophylaxis (SAP) is one of the major purposes of antimicrobial use., Aim: To determine the adherence to the Japanese SAP guidelines in Japanese university hospitals., Methods: This was a retrospective cohort study including 15 general hospitals and one dental university hospital. Up to three cases of 18 designated surgeries were evaluated regarding adherence to Japanese SAP guidelines: selection of antibiotics, timing of administration, re-dosing intervals, and duration of SAP. When all items were appropriate, surgery was defined as 'appropriate'., Findings: In total, 688 cases (22-45 cases per surgery) were included. The overall appropriateness was 46.8% (322/688), and the appropriateness of each surgery ranged from 8.0% (2/25, cardiac implantable electronic device implantation) to 92.1% (35/38, distal gastrectomy). The appropriateness of each item was as follows: pre/intraoperative selections, 78.5% (540/688); timing of administrations, 96.0% (630/656); re-dosing intervals, 91.6% (601/656); postoperative selection, 78.9% (543/688); and duration of SAP, 61.4% (423/688). The overall appropriateness of hospitals ranged from 17.6% (9/51) to 73.3% (33/45). The common reasons for inappropriateness were the longer duration (38.5%, 265/688) and choice of antibiotics with a non-optimal antimicrobial spectrum before/during, and after surgery (19.0%, 131/688 and 16.9%, 116/688, respectively), compared to the guideline., Conclusions: Adherence to the guidelines differed greatly between the surgeries and hospitals. Large-scale multi-centre surveillance of SAP in Japanese hospitals is necessary to identify inappropriate surgeries, factors related to the appropriateness, and incidences of surgical site infections., (Copyright © 2022 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Introduction: We aimed to clarify the genetic background and molecular epidemiology of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) at three geographically separated university hospitals in Japan., Methods: From January 2014 to December 2016, 118 ESBL-producing K. pneumoniae (EPKP) strains that were detected and stored at three university hospitals were collected. Molecular epidemiological analysis was performed using enterobacterial repetitive intergenic consensus (ERIC)-polymerase chain reaction (PCR) and multi-locus sequence typing (MLST). The ESBL type was determined using the PCR-sequence method. The presence of plasmid-mediated fluoroquinolone resistance (PMQR) genes was analyzed by PCR. We compared the relationships between PMQR gene possession/quinolone resistance-determining region (QRDR) mutation and levofloxacin (LVFX)/ciprofloxacin (CPFX) susceptibility., Results: The detection rate of EPKP was 4.8% (144/2987 patients). MLST analysis revealed 62 distinct sequence types (STs). The distribution of STs was diverse, and only some EPKP strains had the same STs. ERIC-PCR showed discriminatory power similar to that of MLST. The major ESBL genotypes were CTX-M-15-, CTX-M-14-, and SHV-types, which were detected in 47, 30, and 27 strains, respectively. Ninety-one out of 118 strains had PMQR genes and 14 out of 65 strains which were not susceptible to CPFX had QRDR mutations, and the accumulation of PMQR genes and QRDR mutations tended to lead to higher minimum inhibitory concentrations (MICs) of LVFX., Conclusions: At three geographically separated university hospitals in Japan, the epidemiology of EPKP was quite diverse, and no epidemic strains were found, whereas CTX-M-14 and CTX-M-15 were predominant., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Campylobacter enteritis (En) is the most frequently diagnosed bacterial En worldwide, including in Japan. Campylobacter spp. can also cause bloodstream infection (BSI), reactive arthritis, and Guillain-Barré syndrome. The purpose of this study was to clarify the characteristics of Campylobacter jejuni strains that cause BSI in comparison with En-causing strains. BSI strains (n = 40) and En strains that caused food poisoning (n = 67) were collected in Japan. Our study revealed that ST-4526 was predominant in BSI strains, and the overall distribution of sequence types was similar in both BSI and En strains. Differences in CPS type distribution might be related to the pathogenesis of bacteremia. Quinolone resistance rates were higher than those reported in previous studies, and strains resistant to both quinolones and tetracyclines were more frequently observed in BSI strains. Finally, we report a case of mixed infection with different STs in BSI., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: The dissemination of difficult-to-treat carbapenem-resistant Enterobacterales (CRE) is of great concern. We clarified the risk factors underlying CRE infection mortality in Japan., Methods: We conducted a retrospective, multicentre, observational cohort study of patients with CRE infections at 28 university hospitals from September 2014 to December 2016, using the Japanese National Surveillance criteria. Clinical information, including patient background, type of infection, antibiotic treatment, and treatment outcome, was collected. The carbapenemase genotype was determined using PCR sequencing. Multivariate analysis was performed to identify the risk factors for 28-day mortality., Results: Among the 179 patients enrolled, 65 patients (36.3%) had bloodstream infections, with 37 (20.7%) infections occurring due to carbapenemase-producing Enterobacterales (CPE); all carbapenemases were of IMP-type (IMP-1: 32, IMP-6: 5). Two-thirds of CPE were identified as Enterobacter cloacae complex. Combination therapy was administered only in 46 patients (25.7%), and the 28-day mortality rate was 14.3%. Univariate analysis showed that solid metastatic cancer, Charlson Comorbidity Index ≥3, bloodstream infection, pneumonia, or empyema, central venous catheters, mechanical ventilation, and prior use of quinolones were significant risk factors for mortality. Multivariate analysis revealed that mechanical ventilation (OR: 6.71 [1.42-31.6], P = 0.016), solid metastatic cancers (OR: 5.63 [1.38-23.0], P = 0.016), and bloodstream infections (OR: 3.49 [1.02-12.0], P = 0.046) were independent risk factors for 28-day mortality., Conclusion: The significant risk factors for 28-day mortality in patients with CRE infections in Japan are mechanical ventilation, solid metastatic cancers, and bloodstream infections., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The spread of third-generation cephalosporin-resistant Gram-negative bacteria is a serious concern in acute and post-acute care settings. This study aimed to understand the epidemiology and molecular background of fecal colonization of resistant Enterobacterales in elderly people., Methods: In December 2015-December 2017, stool or rectal swab samples were collected from 101 elderly patients receiving home care, using long-term care facilities (LTCF), and living in nursing homes repeatedly at 3-9-month intervals. Patient clinical background data were collected from medical records. After phenotypic screening for extended-spectrum β-lactamase (ESBL), AmpC-type β-lactamase or carbapenemase production, drug resistance genes of isolates were analyzed using polymerase chain reaction (PCR). ESBL-producing Escherichia coli isolates obtained from the same patients in repetitive screenings were analyzed using PCR-based ORF typing. Risk factors for persistent carriage of resistant Enterobacterales were analyzed using multivariate analysis., Results: Resistant Enterobacterales isolates were detected in 37 of 101 (36.6%) and 29 of 80 (36.3%) residents in first and second screenings, respectively. ESBL-producing E. coli accounted for 80% isolates, the most common being CTX-M-9-group β-lactamase producers. Molecular epidemiological analysis revealed probable transmissions of ESBL-producing E. coli; 58% of ESBL-producing E. coli colonizers were persistent colonizers at least after 3 -month intervals. Age > 87 years and LTCF residence were independent risk factors for persistent carriage of ESBL-producing E. coli., Conclusions: We showed, for the first time, high persistent colonization rate of ESBL-producing E. coli among elderly people in post-acute care settings with probable horizontal transmission. We also identified significant risk factors for persistent colonization., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Prediction of inpatients with community-acquired pneumonia (CAP) at high risk for severe adverse events (SAEs) requiring higher-intensity treatment is critical. However, evidence regarding prediction rules applicable to all patients with CAP including those with healthcare-associated pneumonia (HCAP) is limited. The objective of this study is to develop and validate a new prediction system for SAEs in inpatients with CAP., Methods: Logistic regression analysis was performed in 1334 inpatients of a prospective multicenter study to develop a multivariate model predicting SAEs (death, requirement of mechanical ventilation, and vasopressor support within 30 days after diagnosis). The developed ALL-COP-SCORE rule based on the multivariate model was validated in 643 inpatients in another prospective multicenter study., Results: The ALL-COP SCORE rule included albumin (< 2 g/dL, 2 points; 2-3 g/dL, 1 point), white blood cell (< 4000 cells/μL, 3 points), chronic lung disease (1 point), confusion (2 points), PaO 2 /F I O 2 ratio (< 200 mmHg, 3 points; 200-300 mmHg, 1 point), potassium (≥ 5.0 mEq/L, 2 points), arterial pH (< 7.35, 2 points), systolic blood pressure (< 90 mmHg, 2 points), PaCO 2 (> 45 mmHg, 2 points), HCO 3 - (< 20 mmol/L, 1 point), respiratory rate (≥ 30 breaths/min, 1 point), pleural effusion (1 point), and extent of chest radiographical infiltration in unilateral lung (> 2/3, 2 points; 1/2-2/3, 1 point). Patients with 4-5, 6-7, and ≥ 8 points had 17%, 35%, and 52% increase in the probability of SAEs, respectively, whereas the probability of SAEs was 3% in patients with ≤ 3 points. The ALL-COP SCORE rule exhibited a higher area under the receiver operating characteristic curve (0.85) compared with the other predictive models, and an ALL-COP SCORE threshold of ≥ 4 points exhibited 92% sensitivity and 60% specificity., Conclusions: ALL-COP SCORE rule can be useful to predict SAEs and aid in decision-making on treatment intensity for all inpatients with CAP including those with HCAP. Higher-intensity treatment should be considered in patients with CAP and an ALL-COP SCORE threshold of ≥ 4 points., Trial Registration: This study was registered with the University Medical Information Network in Japan, registration numbers UMIN000003306 and UMIN000009837., (© 2022. The Author(s).)

Background: Fish consumption may be associated with a low risk of coronary artery disease. We aimed to investigate whether higher fish consumption results in improved lifestyle behaviors and thus lower triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio - a predictor of atherosclerotic cardiovascular disease (ASCVD)., Methods and Results: This cross-sectional study included 2,947 middle-aged Japanese males with no history of ASCVD or lipid-modifying therapy, who presented at the Health Planning Center of Nihon University Hospital between April 2018 and March 2019. We performed an analysis of variance using fish consumption as a categorical variable (0-2 days, 3-4 days, or 5-7 days per week). The serum TG/HDL-C ratio in the 5-7 days fish consumption group was significantly lower than those in the 0-2 and 3-4 days fish consumption groups (p < 0.0001 and p < 0.01, respectively). Multiple regression stepwise analysis revealed that weekly fish consumption negatively and independently determined the TG/HDL-C ratio (β = -0.061, p = 0.001). As fish consumption increased, the proportion of subjects with smoking habits decreased (p = 0.014), those engaging in aerobic exercises and aggressive daily physical activity increased (p < 0.0001 for both), and those with alcohol habit increased (p < 0.0001). In addition, we developed the risk stratification for ASCVD by combining the serum HDL-C level and the serum TG/HDL-C ratio with fish consumption., Conclusion: Increased frequency of fish consumption and improved lifestyle behaviors due to daily fish intake may work additively to lower the serum TG/HDL-C ratio. These associations may explain why high fish consumption is associated with a lower risk of ASCVD. Our findings may help physicians and nutritionists in treating patients with heart diseases and metabolic conditions by recommending a high fish diet in middle-aged Japanese males., (© 2021 S. Karger AG, Basel.)

Background: The high mortality of acute myocardial infarction (AMI) with cardiogenic shock (i.e., Killip class IV AMI) remains a challenge in emergency cardiovascular care. This study aimed to examine institutional factors, including the number of JCS board-certified members, that are independently associated with the prognosis of Killip class IV AMI patients., Methods and results: In the Japanese registry of all cardiac and vascular diseases-diagnosis procedure combination (JROAD-DPC) database (years 2012-2016), the 30-day mortality of Killip class IV AMI patients (n=21,823) was 42.3%. Multivariate analysis identified age, female sex, admission by ambulance, deep coma, and cardiac arrest as patient factors that were independently associated with higher 30-day mortality, and the numbers of JCS board-certified members and of intra-aortic balloon pumping (IABP) cases per year as institutional factors that were independently associated with lower mortality in Killip class IV patients, although IABP was associated with higher mortality in Killip classes I-III patients. Among hospitals with the highest quartile (≥9 JCS board-certified members), the 30-day mortality of Killip class IV patients was 37.4%., Conclusions: A higher numbers of JCS board-certified members was associated with better survival of Killip class IV AMI patients. This finding may provide a clue to optimizing local emergency medical services for better management of AMI patients in Japan.

Higher fish consumption has been reported to be associated with a lower incidence of coronary artery disease. We hypothesized that a higher frequency of fish intake may be associated with lower peripheral white blood cell (WBC) counts, a marker of chronic inflammation, which is known to be involved in the development of atherosclerotic cardiovascular disease (ASCVD), and a healthy lifestyle. This cross-sectional study was conducted between April 2018 and August 2018 at the Health Planning Center of Nihon University Hospital in a cohort of 4105 apparently healthy subjects. The average frequency of fish intake was 2.3 ± 1.3 days per week. The WBC count decreased significantly as the frequency of fish intake (0-2 days, 3-4 days, or 5-7 days per week) increased (s < 0.0001). Multivariate linear regression analysis identified higher weekly frequency of fish intake as a significant independent determinant of a lower WBC count (β =  - 0.051, p = 0.001). Furthermore, as the weekly frequency of fish intake increased, the proportion of habitual cigarette smokers decreased (p = 0.021), that of subjects engaging in habitual aerobic exercises increased (p < 0.0001), and the weekly alcohol intake frequency increased (p < 0.0001). Moreover, the above-mentioned lifestyle behaviors were also independent determinants of the WBC count. These results suggest that a high frequency of fish intake might be associated with healthier lifestyle behaviors as well as lower WBC counts, and thus may both exert beneficial anti-inflammatory effects and represent a component of healthier lifestyle behaviors associated with a lower risk of ASCVD in Japanese. This association may be partially related to the preventive effects of a higher fish intake on ASCVD events. CLINICAL TRIAL REGISTRATION: UMIN ( http://www.umin.ac.jp/ ) Study ID: UMIN000039197 retrospectively registered 1 February 2020.

Background: Pompe disease is an autosomal recessive disorder caused by deficiency of the acid α-glucosidase (GAA) enzyme. GAA deficiency induces progressive glycogen accumulation which leads to weakness of the respiratory muscle including the diaphragm. Pompe disease is one of the few myopathies, for which an established therapy is available. Thus, earlier detection of potential late-onset Pompe disease (LOPD) and earlier intervention would have a significant clinical impact., Purpose: Our hypothesis is that sleep problems including sleep disordered breathing (SDB) and clinical symptoms may indicate an early stage of LOPD since decreased respiratory muscle activity generally first presents during sleep. Thus, the aims of this prospective, multicenter observational cohort study in Japan (PSSAP-J) are to demonstrate a higher prevalence of LOPD in a sleep lab-based population (primary outcome), and to identify predictive factors for LOPD from findings in diagnostic polysomnography (PSG) and clinical symptoms (secondary outcomes)., Methods: The study design is a prospective multicenter observational cohort study. Consecutive patients who present to sleep labs due to suspected SDB for an overnight PSG will be enrolled. All patients will be measured for creatine kinase, GAA activity, and if necessary, genetic analysis of GAA. Furthermore, chest X-ray, pulmonary function test, and arterial blood gas analysis will be collected. Then, prevalence and specific findings of LOPD will be assessed., Result: Congenital myopathy shows a shift from slow-deep to rapid-shallow breathing during transition from wakefulness to sleep accompanying a symptom of waking with gasping (actual further results are pending)., Discussion: The distribution in respiratory physiology between during wakefulness and sleep specific to LOPD may provide insights into early-stage detection., Clinical Trial Registration Number: UMIN000039191, UMIN Clinical Trials Registry ( http://www.umin.ac.jp/ctr ).

Objectives: This study sought to investigate the incidence and characteristics of the real-world safety profile of second-generation cryoballoon ablation (2nd-CBA) in Japan., Background: Pulmonary vein isolation using second-generation cryoballoons is an accepted atrial fibrillation ablation strategy., Methods: This multicenter observational study included 4,173 patients with atrial fibrillation (3,807 paroxysmal) who underwent a 2nd-CBA in 18 participating centers. The baseline data and details of all procedure-related complications within 3 months post-procedure in consecutive patients from the first case at each center were retrospectively collected., Results: Adjunctive ablation after the pulmonary vein isolation was performed in 2,745 (65.8%) patients. Complications associated with the entire procedure were observed in 206 (4.9%) total patients, and in the multivariate analysis, the age (odds ratio: 1.015; 95% confidence interval: 1.001 to 1.030; p = 0.035) and study period were predictors. Air embolisms manifesting as ST-segment elevation and cardiac tamponade requiring drainage occurred in 63 (1.5%) and 15 (0.36%) patients, respectively. Six (0.14%) patients had strokes/transient ischemic attacks, among whom 5 underwent ablation under an interrupted anticoagulation regimen. No atrioesophageal fistulae occurred; however, 10 (0.24%) patients had symptomatic gastric hypomotility. Esophageal temperature monitoring did not reduce the incidence, and the incidence was significantly higher in patients with adjunctive posterior wall isolations or mitral isthmus ablation than those without (p = 0.004). Phrenic nerve injury occurred during the 2nd-CBA in 58 (1.4%) patients; however, all were asymptomatic and recovered within 13 months. One patient died of aspiration pneumonia., Conclusions: This study had a high safety profile of 2nd-CBA despite including the early experience and high rate of adjunctive ablation. Care should be taken for air embolisms during 2nd-CBA., Competing Interests: Funding Support and Author Disclosures This work was supported in part by grants (19K08487, 19K08576) for Cardiovascular Diseases from the Ministry of Health, Labour, and Welfare, Japan (to Drs. Miyazaki and Tada). Dr. Miyazaki has received consulting fees and speaker honoraria from Medtronic; and belongs to the endowed departments of Medtronic, Boston, Abbott, and Japan Lifeline. Dr. Kobori has received speaker honoraria from Medtronic. Dr. Kusano has received speaker honoraria from Daiichi-Sankyo Company, Ltd., Japan, Bristol Myers Squibb, Biotronik Japan, and Medtronic Japan; and has received research grants from Medtronic Japan and EP-CRSU Co., Ltd. Dr. Tada has received speaker honoraria from Daiichi-Sankyo Company, Ltd., Japan, Bristol Myers Squibb, Biotronik Japan, Boehringer Ingelheim Japan, and Johnson & Johnson; and has received research grants from Boehringer Ingelheim Japan, Bayer Yakuhin, Ltd., Japan, and Takeda Pharmaceutical Company, Ltd., Japan. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Growing evidence for the advantages of robotic pancreatoduodenectomy (RPD) has been demonstrated internationally. However, there has been no structured training program for RPD in Japan. Herein, we present the surgical training model of RPD and a standardized protocol for surgical technique., Methods: The surgical training model and surgical technique were standardized in order to implement RPD safely, based on the Dutch training system collaborated with the University of Pittsburgh Medical Center., Results: The surgical training model included various trainings such as basic robotic training, simulation training, biotissue training, and a surgical video review. Furthermore, a standardized protocol on the surgical technique was established to understand the tips, tricks, and pitfalls of RPD., Conclusions: Safe implementation of RPD can be achieved through the completion of a structured training program and learning surgical technique. A nationwide structured training system should be developed to implement the program safely in Japan.

Pseudomonas aeruginosa resistance is a major issue worldwide. Drug resistance is related to inappropriate antibiotic use. Because antipseudomonal agents have a wide spectrum, they must be used appropriately. The purpose of this study was to clarify the trends in antipseudomonal agent use in Japan based on sales data from 2006 to 2015. The total antipseudomonal agent use was increased significantly (r = 0.10, P for trend  = 0.00040). The proportion of fluoroquinolones use was the highest throughout the year, accounting for 88.6-91.4%. The use of piperacillin/tazobactam significantly increased. The increased use of these drugs may be due to the launch of higher doses and additional indications. On the other hand, for antipseudomonal agents, parenteral carbapenems use was 2.7-3.7%, but it has remained unchanged over the years. In Japan, permit and notification systems have been introduced to prevent the inappropriate use of parenteral carbapenems in medical institutions. It was speculated that these efforts suppressed the inappropriate use of parenteral carbapenems. This study clarified the trend of antipseudomonal agent use in Japan from 2006 to 2015. It is important to continue monitoring antipseudomonal agents use to conduct appropriate antimicrobial resistance measures.

Clinical investigators have focused on the real-time evaluation of cerebral blood oxygenation (CBO) by near-infrared spectroscopy (NIRS) during cardiopulmonary resuscitation (CPR). A previous study showed that an abrupt increase of oxy-hemoglobin (Hb) level and tissue oxygenation index (TOI) was associated with the timing of return of spontaneous circulation (ROSC). However, it is not clear how TOI alters before and after CPR including a period of cardiac arrest (CA). Therefore, this study aimed to assess CBO with asphyxia CA and its association with CPR to ROSC in rats. Male Sprague-Dawley rats were used. We attached NIRS (NIRO-200NX, Hamamatsu Photonics, Japan) from the nasion to the upper cervical spine in rats. A ten-minute asphyxia was given to induce CA. After CA, mechanical ventilation was restarted, and manual CPR was performed. We examined the mean arterial pressure (MAP), end-tidal carbon dioxide (ETCO 2 ), and Oxy/Deoxy-Hb and TOI. Out of 14 rats, 11 obtained sustained ROSC. After the induction of asphyxia, a rapid drop of TOI was observed, followed by a subsequent increase of Oxy-Hb, Deoxy-Hb, and TOI with CPR. Recent CPR guidelines suggest the use of ETCO 2 during CPR since its abrupt increase is a reasonable indicator of ROSC. In this study, abrupt increases in MAP, ETCO 2 , and TOI were observed at the time of ROSC. TOI can be an alternative to ETCO 2 for identifying ROSC after CA, and it also has the capability of monitoring CBO during and after CPR.

Background: The prognosis of intrahepatic cholangiocarcinoma (ICC) has been poor, because of the high recurrence rate even after curative surgery. This study aimed to evaluate the prognostic impact of surgical resection of recurrent ICC., Patients and Methods: A total of 345 cases of ICC who underwent hepatectomy with curative intent in 17 institutions were retrospectively analyzed, focusing on recurrence patterns and treatment modalities for recurrent ICC., Results: Median survival time and overall 5-year recurrence-free survival rate were 17.8 months and 28.5%, respectively. Recurrences (n = 223) were classified as early (recurrence at ≤1 year, n = 131) or late (recurrence at >1 year, n = 92). Median survival time was poorer for early recurrence (16.3 months) than for late recurrence (47.7 months, p<0.0001). Treatment modalities for recurrence comprised surgical resection (n = 28), non-surgical treatment (n = 134), and best supportive care (BSC) (n = 61). Median and overall 1-/5-year survival rates after recurrence were 39.5 months and 84.6%/36.3% for surgical resection, 14.3 months and 62.5%/2.9% for non-surgical treatment, and 3 months and 4.8%/0% for BSC, respectively (p<0.0001). Multivariate analysis identified early recurrence, simultaneous intra- and extrahepatic recurrence, and surgical resection of recurrence as significant prognostic factors. In subgroup analyses, surgical resection may have positive prognostic impacts on intra- and extrahepatic recurrences, and even on early recurrence. However, simultaneous intra- and extrahepatic recurrence may not see any survival benefit from surgical management., Conclusion: Surgical resection of recurrent ICC could improve survival after recurrence, especially for patients with intra- or extrahepatic recurrence as resectable oligo-metastases., Competing Interests: The authors have declared that no competing interests exist.

Background: In 2018, the Japanese medical reimbursement system was revised to introduce a fee for the implementation of an antimicrobial stewardship (AS) fee for pediatric patients. The purpose of this study was to evaluate physicians' prescription behavior following this revision., Methods: We conducted a retrospective observational study from January 1, 2017 to September 30, 2018 of pediatric (< 15 years) outpatients with upper respiratory tract infections (URIs). To assess the pattern of antibiotic prescription for the treatment of pediatric URIs before and after the introduction of the AS fee, we extracted data on pediatric URIs, diagnosed during the study period. Patients were divided based on whether medical facilities claimed AS fees. We defined antibiotic use as the number of antibiotics prescribed, and evaluated the proportion of each class to the total number of antibiotics prescribed. We also recorded the number of medical facilities that each patient visited during the study period., Results: The frequency of antibiotic prescription decreased after AS fee implementation, regardless of whether the facility claimed the AS fee, but tended to be lower in facilities that claimed the fee. Additionally, the frequency of antibiotic prescription decreased in all age groups. Despite the reduced frequency of antibiotic prescription, consultation behavior did not change., Conclusions: The AS fee system, which compensates physicians for limiting antibiotic prescriptions, helped to reduce unnecessary antibiotic prescription and is thus a potentially effective measure against antimicrobial resistance.

A 40-year-old Japanese woman presented to our hospital with general fatigue and muscle weakness. She had a history of premature loss of deciduous teeth at 4 years old, her serum alkaline phosphatase (ALP) activity was as low as 91 U/L, and radiologic studies revealed thoracic deformity and sacroiliac calcification. Genetic sequencing revealed a heterozygous c.1559delT mutation in the tissue non-specific alkaline phosphatase gene (ALPL). Based on these findings, she was diagnosed with hypophosphatasia (HPP), and treatment with asfotase alfa, a recombinant human tissue-nonspecific alkaline phosphatase (TNSALP), was initiated. After six months of treatment with asfotase alfa, improvements were observed in the SF-36 score, six-minute walk distance, and grasping power. Although the overdiagnosis needs to be avoided, HPP should be considered in patients with undiagnosed musculoskeletal symptoms and a low serum ALP activity.

In Japan, there is no national surveillance study of Clostridioides (Clostridium) difficile infection (CDI), and details about the epidemiology and treatment status of CDI are unknown. Additionally, clinical practice guidelines (CPGs) for CDI are published by four different institutions. All CPGs recommend that the antimicrobials, vancomycin (VCM) and metronidazole (MNZ), should be selected according to disease severity. However, the trends for VCM and MNZ use in Japan remain unclear. Therefore, this study was aimed at clarifying the secular trends for VCM and MNZ use based on sales data from 2006 to 2015 and discussing its impact on CDI status and drug costs. This is the first study to clarify the antibiotic use trends for CDI treatment. We found that the total use increased over time (r = 0.0013, P for trend  < 0.0001). While VCM use significantly decreased (r = -0.0003, P for trend  = 0.0002), MNZ use increased (r = 0.0017, P for trend  < 0.0001). These results show that although treatment for CDI was in line with CPGs, CDI incidence might be on an increasing trend. Additionally, despite the increased total use, the total drug costs decreased by 55% ($ 25 million) from 2006 to 2015. It was also surmised that CDI treatment in compliance with CPGs would lead to a reduction in drug costs. Hence, to understand the epidemiology of CDI, it is important to continuously investigate the use of drugs used for CDI therapy.

Patterns of the use of anti-methicillin-resistant Staphylococcus aureus (MRSA) agents in Japan might be influenced by the launch of new anti-MRSA agents, the publication of relevant guidelines, and the increase in the number of generic medicines. However, as anti-MRSA agents are included in multiple anatomical therapeutic chemical classifications, such as glycopeptides and aminoglycosides, the trends of the use of individual anti-MRSA agents remain unclear. Here, we aimed to clarify the trends of anti-MRSA agent use in Japan from 2006 to 2015 based on sales data. Total anti-MRSA agent use was found to have significantly increased from 2006 to 2015 (P for trend  = 0.027, r = 0.00022). Individual trends for vancomycin (VCM), daptomycin, and linezolid (LZD) use showed significant increases, while those for arbekacin (ABK) and teicoplanin (TEIC) showed decreases. In addition, oral LZD use significantly increased, while there was no significant change in intravenous LZD use. The ratio of oral LZD use to total LZD use increased from 25.5% in 2006 to 39.9% in 2015. Meanwhile, TEIC and ABK use decreased, while VCM use increased, following the launch of generic medicines. These results might reflect the status of guideline compliance, the launch of new anti-MRSA agents, and the decline in the sales promotion of the original medicines. It is extremely important to investigate trends for the use of not only different antibiotic groups but also individual antibiotics to develop and implement antimicrobial resistance countermeasures.

Background and Aim: Although sporadic non-ampullary duodenal adenoma is speculated to be precancerous lesion, the relationship between adenoma and carcinoma remains unclear due to their rarity. Previous studies on sporadic non-ampullary duodenal epithelial neoplasm (SNADEN) have mainly targeted superficial tumors, like adenoma and early carcinoma. The clinicopathological features, including those of advanced carcinoma, remain poorly investigated. We assessed the clinicopathological features of SNADEN, including advanced carcinoma, focusing on tumor location., Methods: We retrospectively collected the data of 410 patients who had been clinically and pathologically diagnosed with SNADEN at 11 institutions in Japan between June 2002 and March 2014., Results: The SNADEN was mucosal neoplasia and invasive carcinoma in 321 (78.3%) and 89 (21.7%) patients, respectively. The proportion of invasive carcinomas in SNADEN was significantly higher on the oral side of the papilla of Vater (oral-Vater) than on the anal side (anal-Vater) (27.9% vs 14.4%, P < 0.001). Undifferentiated-type carcinoma was significantly more frequent with oral-Vater than anal-Vater (38.7% vs 14.8%, P = 0.026). The recurrence rate of surgically R0 resected locally advanced carcinomas was significantly higher with oral-Vater than anal-Vater (46.4% vs 8.3%, P = 0.021). Furthermore, the relapse-free survival with oral-Vater was significantly shorter than with anal-Vater (hazard ratio: 2.35; 95% confidence interval: 1.09-5.50; P = 0.028)., Conclusions: The clinicopathological features of SNADEN on oral-Vater were different from those on anal-Vater. SNADEN on oral-Vater was more likely to be invasive carcinomas and might behave more aggressively due to biologically higher malignancy than that on anal-Vater., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: To clarify the molecular epidemiology of carbapenem-resistant Enterobacter cloacae complex (CREC) and the risk factors for acquisition of carbapenemase-producing E. cloacae complex (CPEC)., Methods: Using clinical CREC isolates detected in a Japanese university hospital over 4 years, carbapenemase production was screened with phenotypic methods. Carbapenemase genes were analysed by PCR and sequencing. Molecular epidemiological analyses were conducted with repetitive extragenic palindromic (REP)-PCR and multilocus sequence typing (MLST). CRECs were identified to the subspecies level by hsp60 sequencing. Whole-genome sequencing of plasmids was conducted. A case-control study was performed to identify risk factors for acquisition of CPEC among patients with CREC., Results: Thirty-nine CRECs including 20 CPECs carrying bla IMP-1 were identified. Patients with CPEC had longer hospital stay before detection (26.5 days vs. 12 days, p  = 0.008), a urinary catheter (odds ratio [OR], 5.36; 95% confidence interval [CI], 1.14-30.9; p  = 0.023), or intubation (OR, 7.53; 95% CI, 1.47-53.8; p  = 0.008) compared to patients without CPEC. Four genetically closely related CPEC clusters were observed, which showed that three of four CPEC clusters corresponded to E. asburiae (ST 53), E. hormaechei subsp. steigerwaltii (ST 113 and ST 1047) and E. cloacae subsp. cloacae (ST 513) by MLST and hsp60 sequencing. Seven representative plasmids shared structures with class I integron containing bla IMP-1 and IncHI2A replicon type., Conclusions: A longer hospital stay, presence of a urinary catheter, and intubation are risk factors for CPEC acquisition. In addition to horizontal transmission of genetically indistinguishable CPECs, IncHI2A plasmid carrying bla IMP-1 appeared to be transferred among genetically different ECs., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Background: Hospital outbreaks of antimicrobial-resistant (AMR) bacteria should be detected and controlled as early as possible., Aim: To develop a framework for automatic detection of AMR outbreaks in hospitals., Methods: Japan Nosocomial Infections Surveillance (JANIS) is one of the largest national AMR surveillance systems in the world. For this study, all bacterial data in the JANIS database were extracted between 2011 and 2016. WHONET, a free software for the management of microbiology data, and SaTScan, a free cluster detection tool embedded in WHONET, were used to analyse 2015-2016 data of eligible hospitals. Manual evaluation and validation of 10 representative hospitals around Japan were then performed using 2011-2016 data., Findings: Data from 1031 hospitals were studied; mid-sized (200-499 beds) hospitals accounted for 60%, followed by large hospitals (≥500 beds; 24%) and small hospitals (<200 beds; 16%). More clusters were detected in large hospitals. Most of the clusters included five or fewer patients. From the in-depth analysis of 10 hospitals, ∼80% of the detected clusters were unrecognized by infection control staff because the bacterial species involved were not included in the priority pathogen list for routine surveillance. In two hospitals, clusters of more susceptible isolates were detected before outbreaks of more resistant pathogens., Conclusion: WHONET-SaTScan can automatically detect clusters of epidemiologically related patients based on isolate resistance profiles beyond lists of high-priority AMR pathogens. If clusters of more susceptible isolates can be detected, it may allow early intervention in infection control practices before outbreaks of more resistant pathogens occur., (Copyright © 2018 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Consciousness disturbance is one of the major clinical signs associated with shock state, but its prognostic value has not been previously evaluated in cardiovascular shock patients. We aimed to evaluate the prognostic value of neurological status for 30-day mortality in cardiovascular shock patients without out-of-hospital cardiac arrest (OHCA)., Methods and results: Patients with out-of-hospital onset cardiovascular shock were recruited from the Japanese Circulation Society Shock Registry. Neurological status upon hospital arrival was evaluated using the Japan Coma Scale (JCS). Patients were divided into 4 groups according to the JCS: alert, JCS 0; awake, JCS 1-3 (not fully alert but awake without any stimuli); arousable, JCS 10-30 (arousable with stimulation); and coma JCS 100-300 (unarousable). The primary endpoint was 30-day all-cause death. In total, 700 cardiovascular shock patients without OHCA were assessed. The coma group was associated with a higher incidence of 30-day all-cause death compared with other groups (alert, 15.3%; awake, 24.4%; arousable, 36.8%; coma, 48.5%, P<0.001). Similar trends were observed in etiologically divergent subgroups (acute coronary syndrome, non-ischemic arrhythmia, and aortic disease). On multivariate Cox regression analysis, arousable (hazard ratio [HR], 1.82; 95% CI: 1.16-2.85, P=0.009) and coma (HR, 2.72; 95% CI: 1.76-4.22, P<0.001) (reference: alert) independently predicted 30-day mortality., Conclusions: Neurological status upon hospital arrival was useful to predict 30-day mortality in cardiovascular shock patients without OHCA.

Background: Cigarette smoking in patients with asthma leads to poor symptom control. As patients who are current smokers have been excluded from enrollment in many clinical trials on asthma, there are few reports on the treatment in current smokers with asthma. In this study, we aimed to assess how respiratory physicians manage asthma in current smokers in Japan., Methods: Respiratory physicians in 16 Japanese hospitals answered a questionnaire on treatment for patients with asthma between December 2014 and February 2015. Medical records were reviewed for 1756 patients with asthma., Results: The mean patient age was 61.1 years, and 62.9% of the patients were female. A total of 102 patients (5.8%) were current smokers, and 546 patients (31.1%) were former smokers. Long-acting muscarinic antagonists (LAMA) were prescribed more frequently for current smokers with asthma than for former smokers and never smokers with asthma (10.8% vs 4.6%, p = 0.01, 10.8% vs 3.8%, p < 0.01). In contrast, macrolides were prescribed more frequently for former smokers and never smokers with asthma than for current smokers with asthma (7.7% vs 1.0%, p = 0.01, 6.4% vs 1.0%, p = 0.03). Triple therapy, i.e., inhaled corticosteroids, long-acting beta agonists, and LAMA concomitantly, was prescribed for current smokers with asthma more frequently than for former smokers and never smokers with asthma (9.8% vs 4.0%, p = 0.01, 9.8% vs 3.3%, p < 0.01)., Conclusions: According to this survey, current smokers with asthma received more intensive therapy, including LAMA, than did former smokers with asthma., (Copyright © 2018 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

This report described the experience of active surveillance culture implemented in response to the identification of a single carbapenemase-producing Escherichia coli in a Japanese university hospital. It revealed a horizontal transmission event and an additional asymptomatic carrier of carbapenemase-producing Escherichia coli with unique drug susceptibility and resistance gene profiles. Early implementation of active surveillance culture as a part of multifaceted infection control measures appeared to be useful to control further transmission of carbapenemase-producing Escherichia coli even in the low endemic facility. Further investigations on the timing and usefulness of active surveillance culture in the control of carbapenemase-producing Enterobacteriaceae would be warranted., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is one of the ultimately invasive procedures for managing a noncompressive torso injury. Since it is less invasive than resuscitative open aortic cross-clamping, its clinical application is expected., Methods: We retrospectively evaluated the safety and clinical feasibility of REBOA (intra-aortic occlusion balloon, MERA, Tokyo, Japan) using the Seldinger technique to control severe hemorrhage. Of 5,230 patients admitted to our trauma center in Japan from 2007 to 2013, we included 24 who underwent REBOA primarily. The indications for REBOA were a pelvic ring fracture or hemoperitoneum with hemodynamically instability and impending cardiac arrest. Emergency hemostasis was performed during REBOA in all patients., Results: All 24 patients had a blunt injury, the median age was 59 (interquartile range, 41-71 years), the median Injury Severity Score (ISS) was 47 (interquartile range, 37-52), the 30-day survival rate was 29.2% (n = 7), and the median probability survival rate was 12.5%. Indications for REBOA were hemoperitoneum and pelvic ring fracture in 15 cases and overlap in 8 cases. In 10 cases of death, the balloon could not be deflated in 5 cases. In 19 cases in which the balloon was deflated, the median duration of aortic occlusion was shorter in survivors than in deaths (21 minutes vs. 35 minutes, p = 0.05). The mean systolic blood pressure was significantly increased by REBOA (from 53.1 [21] mm Hg to 98.0 [26.6] mm Hg, p < 0.01). There were three cases with complications (12.5%), one external iliac artery injury and two lower limb ischemias in which lower limb amputation was necessary in all cases. Acute kidney injury developed in all three cases, but failure was not persistent., Conclusion: REBOA seems to be feasible for trauma resuscitation and may improve survivorship. However, the serious complication of lower limb ischemia warrants more research on its safety., Level of Evidence: Therapeutic/care management, level V.

Some important virulence factors have been elucidated in Klebsiella pneumoniae infections. We investigated the relationship between virulence factors and multilocus sequence types (STs) and assessed the risk factors for bacteremia in patients with pneumonia due to K. pneumoniae. From April 2004 through April 2012, a total of 120 K. pneumoniae isolates from patients with pneumonia (23 with bacteremia and 97 without bacteremia) were collected from 10 medical institutions in Japan. Additionally, 10 strains of K. pneumoniae serotype K2 that were isolated >30 years ago were included in this study. These isolates were characterized using multilocus sequence typing (MLST), and the characteristics of their virulence factors, such as hypermucoviscosity phenotype and RmpA and aerobactin production between patients with and without bacteremia, were examined. MLST analysis was performed on the 120 isolates from patients with pneumonia, and some sequence type groups were defined as genetic lineages (GLs). GL65 was more prevalent among patients with bacteremia (21.7%) than in those without bacteremia (7.2%). The majority of the strains with serotype K2 were classified into GL14 or GL65, and rmpA and the gene for aerobactin were present in all GL65-K2 strains but absent in all GL14-K2 strains. In a multivariate analysis, the independent risk factors for bacteremia included GL65 (adjusted odds ratio [AOR], 9.46; 95% confidence interval [CI], 1.81 to 49.31), as well as neoplastic disease (AOR, 9.94; 95% CI, 2.61 to 37.92), immunosuppression (AOR, 17.85; 95% CI, 1.49 to 214.17), and hypoalbuminemia (AOR, 4.76; 95% CI, 1.29 to 17.61). GL65 was more prevalent among patients with bacteremia and was associated with the virulence factors of K. pneumoniae., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Recently, liver transplantation (LT) has been increasingly performed for unresectable hepatoblastoma (HB) with acceptable results. We conducted a national survey of cases undergoing living donor liver transplantation (LDLT) for HB to evaluate their outcomes. Thirty-nine patients (28 males and 11 females with a median age at LDLT of 3.6 years) who had undergone LDLT for HB by the end of 2009 were enrolled in this study. The clinical data were collected from their medical records via a questionnaire survey in 2011 (median follow-up = 4.6 years). Thirteen patients (33.3%) had extrahepatic lesions before LDLT. Thirty-eight patients (97.4%) received chemotherapy, and 15 (38.5%) underwent hepatectomy before LDLT. Twenty-seven patients (69.2%) were alive without recurrence after LDLT, and 12 patients (30.8%) suffered from recurrence. The most common site of recurrence was the lung (9 cases), which was followed by the graft liver (6 cases). The median interval from LDLT to recurrence was 5.5 months. Four of the 9 cases (44.4%) with lung metastasis underwent surgical resection, and 3 were alive without any tumor recurrence. Eight patients died because of tumor recurrence. The multivariate landmark analysis revealed that the independent recurrence risk factors were a high alpha-fetoprotein (AFP) level at diagnosis [≥ 500,000 ng/mL; hazard ratio (HR) = 7.86, P = 0.010], the presence of extrahepatic lesions before LDLT (HR = 3.82, P = 0.042), and a high AFP level at LDLT (≥ 4000 ng/mL; HR = 9.19, P = 0.036). The actuarial 3- and 5-year patient survival rates were 84.3% and 77.3%, respectively. In conclusion, with appropriate timing for scheduled LT, LDLT provides a valuable alternative treatment with excellent results for children with HB.

Background: There are few large-scale epidemiologic studies examining the associations between sleep problems, gastroesophageal reflux disease (GERD) symptoms, lifestyle and food habits and problem behaviors (PB) in adolescents. The aim of this study was to evaluate the associations among these factors in Japanese adolescents., Methods: A cross-sectional survey of 1840 junior high school students was carried out using questionnaires. The subjects were classified into PB or normal behavior (NB) groups using the Pediatric Symptom Checklist (PSC). The scores of the sleep-related factors, sleep bruxism, lifestyle and food habits, and GERD symptoms were compared. Logistic regression analysis was used to determine the factors related to PB., Results: Mean subject age was 13.3 ± 1.8 years. The PB group had significantly longer sleep latency and higher GERD symptom score (P < 0.001). Furthermore, the PB group was significantly more likely to experience absence of the mother at dinner time, skip breakfast, and have <30 min of conversation among family at dinner time. The PB group had significantly higher frequencies of sleep bruxism, difficulty falling asleep within 30 min, nightmares, feeling of low sleep quality, daytime somnolence, and daytime lack of motivation. Feelings of low sleep quality had the strongest association with PB, with an adjusted odds ratio of 12.88 (95% confidence interval: 8.99-18.46)., Conclusions: PB in adolescents are associated with sleep problems, including sleep bruxism, as well as lifestyle and food habits and GERD symptoms., (© 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.)

Rationale: Identification of patients with drug-resistant pathogens at initial diagnosis is essential for treatment of pneumonia., Objectives: To elucidate clinical features of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP), and to clarify risk factors for drug-resistant pathogens in patients with CAP and HCAP., Methods: A prospective observational study was conducted in hospitalized patients with pneumonia at 10 institutions in Japan. Pathogens identified as not susceptible to ceftriaxone, ampicillin-sulbactam, macrolides, and respiratory fluoroquinolones were defined as CAP drug-resistant pathogens (CAP-DRPs)., Measurements and Main Results: In total, 1,413 patients (887 CAP and 526 HCAP) were analyzed. CAP-DRPs were more frequently found in patients with HCAP (26.6%) than in patients with CAP (8.6%). Independent risk factors for CAP-DRPs were almost identical in patients with CAP and HCAP. These included prior hospitalization (adjusted odds ratio [AOR], 2.06; 95% confidence interval [CI], 1.23-3.43), immunosuppression (AOR, 2.31; 95% CI, 1.05-5.11), previous antibiotic use (AOR, 2.45; 95% CI, 1.51-3.98), use of gastric acid-suppressive agents (AOR, 2.22; 95% CI, 1.39-3.57), tube feeding (AOR, 2.43; 95% CI, 1.18-5.00), and nonambulatory status (AOR, 2.45; 95% CI, 1.40-4.30) in the combined patients with CAP and HCAP. The area under the receiver operating characteristic curve for counting the number of risk factors was 0.79 (95% CI, 0.74-0.84)., Conclusions: The clinical profile of HCAP was different from that of CAP. However, physicians can predict drug resistance in patients with either CAP or HCAP by taking account of the cumulative number of the risk factors. Clinical trial registered with https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000004001&language=E ; number UMIN000003306.

Background and Objectives: The phenomena of periodic cycles of vascular engorgement on the nasal cavity mucosa that alternate between right and left sides are termed the "nasal cycle." The physiologic mechanisms underlying this cycle have not been entirely clarified, even more so during sleep. In this study, we measured the periodic patterns of the normal nasal cycle, not only during wakefulness but also during sleep., Study Design Case Series Methods: Our team utilized a method for functional rhinologic assessment, the portable rhinoflowmeter (Rhinocycle, Rhinometrics, Lynge, Denmark), measuring airflow independently through each nostril during 24 hours on 20 healthy subjects aged 20 to 56 years, and without any nasal pathology or diagnosed medical, psychiatric, or sleep disorders. In addition, a nocturnal polysomnogram was simultaneously performed during sleep., Results: Nineteen of 20 subjects showed a detectable nasal cycle, and 16 of 19 subjects presented a change of the cyclic phase during sleep. The mean nasal cycle duration was 234.2 ± 282.4 minutes (median, 164.1 minutes), although variation was considerable. The mean cycle duration time during sleep was significantly longer than that in wakefulness (P <0.005). The reversal of cyclic phase during sleep tended to be associated with REM sleep (68.8%) and postural changes (18.8%). It never occurred in slow-wave sleep., Conclusions: Nasal cycle duration during sleep is longer than in wakefulness. Changes in laterality of nasal cycle frequently coincide with switches in posture, tend to occur in REM sleep, never occur in slow-wave sleep, and may be absent in subjects with severe nasal septal deviations., (© 2012 The American Laryngological, Rhinological and Otological Society, Inc.)

The CROMIS AhR kit, a simple and rapid yeast bioassay kit, was developed and used to detect dioxins and dioxin-like compounds in 20 gas and solid samples collected from refuse incineration plants in Japan. The World Health Organization toxic equivalent (WHO-TEQ) values of the samples were also calculated using high-resolution gas chromatography/high--resolution mass spectrometry. The WHO-TEQ values of the samples varied greatly, ranging from 0.0021-6.3 ng/g to 0.00013-16 ng/m(3)N (normal cubic meter) in the solid and gas samples, respectively. 2,3,4,7,8-Pentachlorodibenzofuran (23478-PeCDF) and 1,2,3,7,8-pentachlorodibenzo-p-dioxin (12378-PeCDD) were the major contributors to the samples' WHO-TEQ values. The yeast in the bioassay responded to these congeners, and the EC50 values of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2378-TeCDD), 12378-PeCDD, and 2,3,4,7,8-PeCDF were 490, 560, and 590 nM, respectively. The incinerator samples were subjected to the bioassay to obtain 2378-TeCDD equivalent values (CROMIS-TEQ values). The CROMIS-TEQ values of the solid and gas samples ranged from 0.0019 to 5.64 ng/g and from 0.14 to 20 ng/m(3)N, respectively. The CROMIS-TEQ and WHO-TEQ values displayed good correlations (r (2) = 0.94 and 0.95 in the solid and gas samples, respectively), except for those of the samples with low dioxin concentrations (below the Japanese emission standards). Therefore, the CROMIS AhR kit is a useful tool for the initial screening of samples containing dioxin-like compounds.

Background: Surgical site infections (SSIs), particularly organ/space SSIs, remain a common cause of major morbidity after hepatectomy for hepatocellular carcinoma (HCC)., Methods: Risk factors for SSIs were analyzed in 359 patients who underwent hepatectomy for HCC between 2001 and 2010. The causative bacteria, management, outcome, and characteristics of organ/space SSIs were investigated., Results: Anatomic hepatectomy was performed for 296 patients (82.5%), and repeat hepatectomy was carried out for 59 patients (16.4%). SSIs developed in 52 patients (14.5%; incisional, 24 cases; organ/space, 31 cases [3 patients showed both incisional and organ/space SSIs]). No in-hospital mortality related to incisional or organ/space SSIs was encountered. Independent risk factors for SSIs were repeat hepatectomy and operative time ≥ 280 min. Independent risk factors for organ/space SSIs were repeat hepatectomy and bile leakage. Methicillin-resistant Staphylococcus aureus was detected more frequently in organ/space SSIs after repeat hepatectomy than after initial hepatectomy., Conclusions: Repeat hepatectomy and bile leakage represent independent risk factors for organ/space SSIs after hepatectomy for HCC. Establishing treatment strategies is important for preventing postoperative bile leakage and reducing the high rate of organ/space SSIs after repeat hepatectomy.

The Ambulatory Blood Pressure Control and Home Blood Pressure (Morning and Evening) Lowering By N-Channel Blocker Cilnidipine (ACHIEVE-ONE) trial is a large-scale clinical study on blood pressure (BP) and pulse rate (PR) in the real world with use of cilnidipine, a unique L/N-type Ca channel blocker, possessing a suppressive action on increased sympathetic activity in patients with essential hypertension. The effects of cilnidipine on morning hypertension were examined. The authors examined 2319 patients treated with cilnidipine for 12 weeks. Clinic systolic BP (SBP) decreased by 19.6 mm Hg from 155.0 mm Hg, whereas morning SBP decreased by 17.0 mm Hg from 152.9 mm Hg after 12-week cilnidipine treatment. Cilnidipine reduced both morning SBP and PR more markedly in patients with higher baseline morning SBP (-3.2 mm Hg and -1.3 beats per minute in the first quartile of morning SBP, -30.9 mm Hg and -3.2 beats per minute in the fourth quartile), and also reduced both morning PR and SBP more markedly in patients with higher baseline morning PR (0.6 beats per minute and -15.6 mm Hg in <70 beats per minute, and -9.7 beats per minute and -20.2 mm Hg in ≥85 beats per minute). Cilnidipine significantly reduced BP and PR in hypertensive patients at the clinic and at home, especially with higher BP and PR in the morning., (© 2012 Wiley Periodicals, Inc.)

Plasmid-mediated AmpC β-lactamase-producing Escherichia coli (AmpC-E) bacteraemia was characterized by comparison with bacteraemia caused by extended-spectrum β-lactamase (ESBL)-producing E. coli (ESBL-E) and non-resistant E. coli (NR-E) in the era of the worldwide spread of the CTX-M-15-producing O25b-ST131-B2 clone. Of 706 bloodstream E. coli isolates collected between 2005 and 2010 in three Japanese university hospitals, 111 ESBL screening-positive isolates were analysed for AmpC and ESBL genes by PCR. A case-control study was performed in which the cases consisted of all of the patients with AmpC-E bacteraemia. Phylogenetic groups, sequence types and O25b serotype were determined. Twenty-seven AmpC-E isolates (26 of which were of the CMY-2 type) were identified, and 54 ESBL-E and 54 NR-E isolates were selected for the controls. Nineteen AmpC-E isolates were also positive for ESBL. CTX-M-14 was the most prevalent ESBL type among both the AmpC-E and ESBL-E isolates. The O25b-ST131-B2 clone was the most prevalent among the ESBL-E isolates (26%) and the second most prevalent among the NR-E isolates (13%), but only one O25b-ST131-B2 clone was found among the AmpC-E isolates. Twenty-three different sequence types were identified among the AmpC-E isolates. When compared with bacteraemia with ESBL-E, previous isolation of multidrug-resistant bacteria and intravascular catheterization were independently associated with a lower risk for AmpC-E. When compared with NR-E bacteraemia, prior use of antibiotics was the only significant risk factor for AmpC-E. Unlike the spread of the O25b-ST131-B2 clone between ESBL-E and NR-E, the AmpC-E isolates were not dominated by any specific clone., (© 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.)

The contents of six vitamin B6 forms, pyridoxine-β-glucoside, and 4-pyridoxic acid in mature milk of 20 Japanese lactating women consuming ordinary Japanese foods were determined by a 4-pyridoxolactone-conversion HPLC method. These compounds were determined with the average recovery rate of 83.9% or more. The average total content of vitamin B6 forms was 1.01 ± 0.32 (µmol/L). Pyridoxal and pyridoxal 5'-phosphate were found in all of the samples, and their average contents were 0.71 ± 0.28 (µmol/L) and 0.16 ± 0.07 (µmol/L), respectively. Pyridoxamine, pyridoxine, pyridoxamine 5'-phosphate, pyridoxine 5'-phosphate, and pyridoxine-β-glucoside were found in 15, 14, 13, 9, and 7 samples, respectively. The presence of pyridoxine 5'-phosphate was for the first time found in human milk. A method for the determination of 4-pyridoxic acid, which is the excretion form of vitamin B6, was modified to quantitate it by isocratic HPLC. 4-Pyridoxic acid was found in all samples, and its average content was 0.094 ± 0.040 (µmol/L), which was only 12% of its content in cow (Holstein) milk. The total content of vitamin B6 forms, and predominant presence of pyridoxal among other vitamin B6 forms in the Japanese women's milk samples shared similar characteristics with American women's milk samples.

Background: We reported an increased occurrence of cardiovascular diseases (CVDs) after the Great East Japan Earthquake by examining ambulance records, but it had to be confirmed by cardiologists., Methods and Results: We enrolled patients admitted to the cardiology department of the 10 hospitals in the disaster area from 4 weeks prior to 15 weeks after March 11 in the years 2008-2011 (n=14,078). The weekly occurrence of several CVDs, including heart failure (HF), pulmonary thromboembolism (PTE) and infectious endocarditis (IE), was sharply and significantly increased after the Earthquake., Conclusions: The Disaster caused significantly increases in the occurrence of HF, PTE and IE.

Introduction: Living donor hepatectomy is important because it determines donor safety and recipient outcome., Methods: We applied the counter-clockwise liver rotation method and the hanging maneuver from an early stage in two major types of living donor operations., Result: Twenty-eight living donors underwent these procedures with significant reduction in blood loss. Right hepatectomy was performed in 14 of the donors and extended left hepatectomy was performed in the other 14 donors., Conclusion: These techniques facilitate safe and bloodless living donor hepatectomy.