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Objectives: The treatment options available for infections caused by multidrug-resistant Gram-negative pathogens are often limited. Cefiderocol (CFDC) is a novel siderophore cephalosporin that exhibits activity against these pathogens. Several studies have reported the in vitro activity of CFDC against isolates from Europe, the United States, and China, but the activity against carbapenem-resistant bacteria with IMP-type carbapenemase has not been extensively studied. We, therefore, studied the in vitro activities of CFDC against carbapenem-resistant bacteria with available genomic backgrounds based on whole-genome sequencing (WGS) in Japan, where the IMP-type is the predominant carbapenemase produced by Gram-negative rods., Methods: We selected 603 isolates (528 Enterobacterales, 18 Pseudomonas aeruginosa, and 57 Acinetobacter spp.) from a collection of Gram-negative clinical isolates collected during a Japan Antimicrobial Resistance Bacterial Surveillance program and evaluated the antimicrobial activities of CFDC, ceftolozane/tazobactam (CTLZ/TAZ), imipenem-relebactam (IPM/REL), and ceftazidime/avibactam (CAZ/AVI) against carbapenemase-producing Enterobacterales, carbapenemase-non-producing meropenem-non-susceptible Enterobacterales, and carbapenemase-producing nonfermentative bacteria., Results: Among these, 97.7% of carbapenemase-producing Enterobacterales (99.2% of IMP-type carbapenemase-producing Enterobacterales), 100% of carbapenemase-producing P. aeruginosa, and 91.2% of carbapenemase-producing Acinetobacter spp. were susceptible to CFDC, showing better antimicrobial activity than the other antimicrobial agents evaluated in this study. CFDC was highly effective against class A-, B-, and D β-lactamase-harbouring isolates when compared to the other antimicrobial agents. In addition, the relationship between CFDC resistance and three genetic factors involved in resistance was discussed., Conclusions: This is the first large-scale study to systematically demonstrate the efficacy of CFDC against IMP-type carbapenemase-producing strains with known genomic backgrounds., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Effective bystander cardiopulmonary resuscitation (CPR) improves outcomes in out-of-hospital cardiac arrest (OHCA) patients. However, the effect of CPR training on the rate of return of spontaneous circulation (ROSC) among laypersons has yet to be thoroughly evaluated., Methods: This prospective, multicenter observational study was conducted across 42 centers in Japan. We assessed OHCA patients who received bystander CPR from a layperson, excluding those performed by healthcare staff. The primary outcome was the ROSC rate. Secondary outcomes included pre-hospital ROSC, ROSC after hospital arrival, favorable neurological outcomes, and 30-day survival. Propensity score with inverse probability treatment weighting (IPTW) was used to adjust for confounders, including age, sex, presence or absence of witnesses, and past medical history., Results: A total of 969 OHCA patients were included, divided into CPR-trained (n = 322) and control (n = 647). Before adjustment, the ROSC rate was higher in the trained group than the control (40.1% vs. 30.1%, P < 0.01). After IPTW adjustment, the trained group showed a significantly higher ROSC rate (36.7% vs. 30.6%; P = 0.02). All secondary outcomes in the trained group were significantly improved before adjustment. After IPTW adjustment, the trained group showed improved rates of pre-hospital ROSC and ROSC after hospital arrival (30.7% vs. 24.0%; P < 0.01, 23.9% vs. 20.7%; P = 0.04). There were no differences in neurological outcomes and 30-day survival., Conclusion: This study demonstrated that CPR training for laypersons was associated with increased ROSC rates in OHCA patients, indicating potential advantages of CPR training for non-healthcare professionals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type 2 diabetes; however, their effect on arrhythmias is unclear. The purpose of this study was to investigate the effects of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes., Methods: A total of 150 patients with type 2 diabetes who were treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator (ICD/CRT-D) were randomized to once-daily empagliflozin or placebo for 24 weeks. The primary endpoint was the change in the number of ventricular arrhythmias from the 24 weeks before to the 24 weeks during treatment. Secondary endpoints included the change in the number of appropriate device discharges and other values., Results: In the empagliflozin group, the number of ventricular arrhythmias recorded by ICD/CRT-D decreased by 1.69 during treatment compared to before treatment, while in the placebo group, the number increased by 1.79. The coefficient for the between-group difference was - 1.07 (95% confidence interval [CI] - 1.29 to - 0.86; P < 0.001). The change in the number of appropriate device discharges during and before treatment was 0.06 in the empagliflozin group and 0.27 in the placebo group, with no significant difference between the groups (P = 0.204). Empagliflozin was associated with an increase in blood ketones and hematocrit and a decrease in blood brain natriuretic peptide and body weight., Conclusions: In patients with type 2 diabetes treated with ICD/CRT-D, empagliflozin reduces the number of ventricular arrhythmias compared with placebo. Trial registration jRCTs031180120., (© 2024. The Author(s).)

Japan is a country with an approximate 10% prevalence rate of carbapenem-resistant Pseudomonas aeruginosa (CRPA). Currently, a comprehensive overview of the genotype and phenotype patterns of CRPA in Japan is lacking. Herein, we conducted genome sequencing and quantitative antimicrobial susceptibility testing for 382 meropenem-resistant CRPA isolates that were collected from 78 hospitals across Japan from 2019 to 2020. CRPA exhibited susceptibility rates of 52.9%, 26.4%, and 88.0% against piperacillin-tazobactam, ciprofloxacin, and amikacin, respectively, whereas 27.7% of CRPA isolates was classified as difficult-to-treat resistance P. aeruginosa . Of the 148 sequence types detected, ST274 (9.7%) was predominant, followed by ST235 (7.6%). The proportion of urine isolates in ST235 was higher than that in other STs ( P = 0.0056, χ 2 test). Only 4.1% of CRPA isolates carried the carbapenemase genes: bla GES (2) and bla IMP (13). One ST235 isolate carried the novel bla IMP variant bla IMP-98 in the chromosome. Regarding chromosomal mutations, 87.1% of CRPA isolates possessed inactivating or other resistance mutations in oprD . The findings from this study and other surveillance studies collectively demonstrate that CRPA exhibits marked genetic diversity and that its multidrug resistance in Japan is less prevailed than in other regions. This study contributes a valuable data set that addresses a gap in genotype/phenotype information regarding CRPA in the Asia-Pacific region, where the epidemiological background markedly differs between regions.mexR , nalC , and nalD ) for the MexAB-OprM efflux pump. Additionally, 4.7% of CRPA isolates carried a resistance mutation in the PBP3-encoding gene ftsI . The findings from this study and other surveillance studies collectively demonstrate that CRPA exhibits marked genetic diversity and that its multidrug resistance in Japan is less prevailed than in other regions. This study contributes a valuable data set that addresses a gap in genotype/phenotype information regarding CRPA in the Asia-Pacific region, where the epidemiological background markedly differs between regions., Competing Interests: The authors declare no conflict of interest.

In this study using computed tomography (CT), the volumes of the internal cranial cavities, such as the braincase, frontal sinus and tympanic cavity, and the ratio of the volume of each cavity to the skull volume in Japanese wolves were quantified, and CT images of the frontal sinus were observed. The results were then compared with those of other wolf subspecies, including Akita, a dog breed, to clarify the characteristics of the internal cranial cavities in Japanese wolves. The present study revealed that the Japanese wolf had a relatively larger braincase volume and a relatively smaller frontal sinus volume than the wolf ssp. (a group of wild wolf subspecies except the Japanese wolf) and Akita. Moreover, the relative and absolute tympanic cavity volumes of the Japanese wolf and Akita were significantly smaller than those of the wolf ssp. In the CT image or macroscopic observations, the frontal sinuses of the wolf ssp. and Akita were relatively well developed to the caudal and dorsal directions, respectively, compared with that of the Japanese wolf, and the tympanic cavity of the wolf ssp. was more largely swelled ventrally and medially than that of other groups.

Background: In the chain of survival for Out-of-hospital cardiac arrest (OHCA), each component of care contributes to improve the prognosis of the patient with OHCA. The SARS-CoV-2 (COVID-19) pandemic potentially affected each part of care in the chain of survival. The aim of this study was to compare prehospital care, in-hospital treatment, and outcomes among OHCA patients before and after the COVID-19 pandemic., Methods: We analyzed data from a multicenter prospective study in Kanto area, Japan, named SOS-KANTO 2017. We enrolled patients who registered during the pre-pandemic period (September 2019 to December 2019) and the post-pandemic period (June 2020 to March 2021). The main outcome measures were 30-day mortality and the proportion of favorable outcomes at 1 month, and secondary outcome measures were changes in prehospital and in-hospital treatments between the pre- and post-pandemic periods., Results: There were 2015 patients in the pre-pandemic group, and 5023 in the post-pandemic group. The proportion of advanced airway management by emergency medical service (EMS) increased (p < 0.01), and EMS call-to-hospital time was prolonged (p < 0.01) in the post- versus pre-pandemic group. There were no differences between the groups in defibrillation, extracorporeal membrane oxygenation, or temperature control therapy (p = 0.43, p = 0.14, and p = 0.16, respectively). Survival rate at 1 month and favorable outcome rate at 1 month were lower (p = 0.01 and p < 0.01, respectively) in the post- versus pre-pandemic group., Conclusion: Survival rate and favorable outcome rate 1 month after return of spontaneous circulation of OHCA worsened, EMS response time was prolonged, and advanced airway management by EMS increased in the post- versus pre-pandemic group; however, most prehospital and in-hospital management did not change between pre- and post-COVID-19 pandemic., (© 2024. The Author(s).)

Background: Out-of-hospital cardiac arrest (OHCA) is a serious condition. The volume-outcome relationship and various post-cardiac arrest care elements are believed to be associated with improved neurological outcomes. Although previous studies have investigated the volume-outcome relationship, adjusting for post-cardiac arrest care, intra-class correlation for each institution, and other covariates may have been insufficient., Objective: To investigate the volume-outcome relationships and favorable neurological outcomes among OHCA cases in each institution., Methods: We conducted a prospective observational study of adult patients with non-traumatic OHCA using the OHCA registry in Japan. The primary outcome was 30-day favorable neurological outcomes, and the secondary outcome was 30-day survival. We set the cutoff values to trisect the number of patients as equally as possible and classified institutions into high-, middle-, and low-volume. Generalized estimating equations (GEE) were performed to adjust for covariates and within-hospital clustering., Results: Among the 9909 registry patients, 7857 were included. These patients were transported to either low- (2679), middle- (2657), or high- (2521) volume institutions. The median number of eligible patients per institution in 19 months of study periods was 82 (range, 1-207), 252 (range, 210-353), and 463 (range, 390-701), respectively. After multivariable GEE using the low-volume institution as a reference, no significant difference in odds ratios and 95% confidence intervals were noted for 30-day favorable neurological outcomes for middle volume [1.22 (0.69-2.17)] and high volume [0.80 (0.47-1.37)] institutions. Moreover, there was no significant difference for 30-day survival for middle volume [1.02 (0.51-2.02)] and high volume [1.09 (0.53-2.23)] institutions., Conclusion: The patient volume of each institution was not associated with 30-day favorable neurological outcomes. Although this result needs to be evaluated more comprehensively, there may be no need to set strict requirements for the type of institution when selecting a destination for OHCA cases., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In breast cancer surgery, some medical facilities lack the necessary resources to conduct sentinel lymph node biopsy and its intraoperative frozen section consultation. In the coastal rural area of Fukushima, Japan, which has suffered from physician undersupply following the 2011 triple disaster of earthquake, tsunami and nuclear disaster, we explored the feasibility of telepathology by evaluating the diagnostic accuracy in remote intraoperative frozen section consultation of sentinel lymph node biopsy and its required time. Although examination time has room for improvement, telepathology can be one possible solution in resource-limited areas.

A nationwide survey of SARS-CoV-2 antinucleocapsid seroprevalence among blood donors in Japan revealed that, as of November 2022, infection-induced seroprevalence of the population was 28.6% (95% CI 27.6%-29.6%). Seroprevalence studies might complement routine surveillance and ongoing monitoring efforts to provide a more complete real-time picture of COVID-19 burden.

Background: Surgical site infections (SSIs) are among the most common healthcare-associated infections. Laparoscopy is increasingly being used in various surgical procedures. However, no study has examined the association between the proportion of laparoscopic procedures and the incidence of SSIs in digestive surgery using nationwide surveillance data., Methods: We retrospectively investigated national SSI surveillance data from the Japan Nosocomial Infections Surveillance between 2009 and 2019. The annual trend of the SSI rate and the proportion of laparoscopic procedures were assessed, focusing on five major digestive surgeries. This was based on data from 109,544 (appendix surgery), 206,459 (gallbladder surgery), 60,225 (small bowel surgery), 363,677 (colon surgery), and 134,695 (rectal surgery) procedures. The effect of a 10% increase in the proportion of laparoscopic procedures on the reduction of the SSI rate was estimated using mixed-effect logistic regression., Findings: The average SSI rate of the five digestive surgeries decreased from 11.8% in 2009 to 8.1% in 2019. The proportion of laparoscopic procedures in each of the five digestive surgeries increased continuously (p<0.001). The SSI rate for laparoscopic procedures was always lower than that for open procedures. The results were consistent between all and core hospitals participating in the surveillance. The odds ratios of the 10% increase in the proportion of laparoscopic procedures for five digestive surgeries were always <0.950 (p<0.001)., Conclusion: An increase in the proportion of laparoscopic procedures was associated with a reduction in the SSI rate in digestive surgeries., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kajihara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In the prostate gland of the raccoon (Procyon lotor), the morphological appearance of the epithelial cells, such as basal and luminal cells, and the expressions of p63, androgen receptor (AR), and proliferating cell nuclear antigen (PCNA) were examined histologically and immunohistochemically to clarify their seasonal dynamics throughout the year. In this study, the regression with luminal cell defluxion and the regeneration process of the prostatic glandular epithelium was revealed in the seasons with declined spermatogenesis (June to August). The expression of p63 was observed only in the basal cells. AR immunoreactivity in the luminal cells was shown in the developed and regenerating (close to developed) prostates, whereas the basal cells exhibited AR immunoreactivity all year round. PCNA expression was rare in epithelial cells of the developed prostate gland. In the regressed gland, the basal cells demonstrated proliferative ability, whereas PCNA of the luminal cells appeared for the first time in the regenerating phase. This study is the first to clarify the regression with luminal cell defluxion and restoration and the seasonal dynamics of AR expression and proliferative activity in the prostate gland of seasonal breeders.

Objective: In elderly populations, the enlargement of the perivascular space is related to small vessel disease and the glymphatic system. Enlarged perivascular spaces (EPVS) in the basal ganglia (EPVS-BG) and EPVS in the centrum semiovale (EPVS-CSO) are associated with different pathophysiological processes. However, the prevalence of EPVS and the factors associated with EPVS location in healthy middle-aged individuals are still unclear. We aimed to determine the prevalence of EPVS and the factors associated with EPVS location among healthy individuals in their 40 s METHODS: This study included 5000 consecutive healthy individuals who underwent screening for brain diseases in Japan from August to December 2018. Of them, the data of individuals in their 40 s were extracted and analyzed. The associations of age, sex, body mass index, smoking and drinking history, and medical history with EPVS location were investigated. Similar analyses were performed for the other age groups. A literature review on the factors associated with EPVS location was also performed., Results: A total of 1720 individuals in their 40 s were finally included. The prevalence of EPVS-BG and EPVS-CSO was 7.7% and 9.2%, respectively. Age (years), smoking history, and hypertension were associated with EPVS-BG; none of the studied factors were found to be associated with EPVS-CSO. In the elderly, the factors previously reported to be associated with EPVS-BG included atherosclerosis change, while the factors associated with EPVS-CSO were cerebral amyloid angiopathy-related formation., Conclusion: Both EPVS-BG and EPVS-CSO occurred among healthy individuals in their 40 s, but they did so rarely, and less prevalently than in older age groups. EPVS-BG and EPVS-CSO may represent early imaging signs of the atherosclerotic and cerebral amyloid angiopathy processes, respectively., Data Availability: The anonymized data for this study will be shared upon any qualified investigator's request to the corresponding author. Primary data from this study will be made available upon reasonable request in accordance with the review board of the research institute., Competing Interests: Declaration of Competing Interest Dr. Kitamura receives personal fees from Medical Network Systems, MNES Inc., related to this work. Mr. Tomoaki Hamano, as the CEO of SmartScan, Inc., receives officers' remuneration from SmartScan, Inc., and holds more than 5% of SmartScan shares. All the other authors report that they have no conflict of interest to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The increasing incidence of candidemia and the emergence of drug-resistant Candida species are major concerns worldwide. Therefore, long-term surveillance studies are required. Here, we provide one of the largest longitudinal overviews of the trends in the prevalence of Candida species using national data of 57 001 candidemia isolates obtained from > 2000 hospitals for the 2010-2019 period in the Japan Nosocomial Infections Surveillance database. The proportion of Candida species, except Candida krusei and Candida guilliermondii, was almost the same during the study period. The proportion of C. guilliermondii surpassed that of C. krusei in 2014. The incidence of candidemia due to C. albicans (P < 0.0001), C. parapsilosis (P = 0.0002), and C. tropicalis (P < 0.0001) have decreased significantly over this period. Azole susceptibility of C. tropicalis was low, with 17.8% of isolates resistant to fluconazole and 13.5% resistant to voriconazole. The micafungin susceptibility of C. glabrata was low, with 8.0% of isolates showing resistance. The resistance rate of C. krusei toward amphotericin B fluctuated considerably (between 3.2% and 35.7%) over this period. The incidence rate of candidemia caused by C. parapsilosis and C. guilliermondii in hospitals responsible for bone marrow transplantation was significantly higher than that in other hospitals. Overall, our study suggests that in Japan, the species distribution of Candida was almost the same in this period and similar to that reported in North America and Europe. A relatively high resistance to azoles and micafungin was observed in C. glabrata, C. tropicalis, and C. krusei isolates, which require continued surveillance., (© The Author(s) 2022. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Wild boars (Sus scrofa) captured or found dead in Nagano Prefecture were surveyed for antibodies to Aujeszky's disease virus (ADV), Erysipelothrix rhusiopathiae, porcine reproductive and respiratory syndrome virus (PRRSV), and Toxoplasma gondii. While all 168 samples tested were negative for anti-ADV antibodies and all 140 samples tested were negative for anti-PRRSV antibodies, all 190 samples tested were positive for anti-E. rhusiopathiae antibodies and 12 of 180 samples were positive for anti-toxoplasma antibodies. These results suggest that since E. rhusiopathiae and T. gondii cause zoonotic diseases, in addition to wild boars being a potential source of infection for domestic pigs, caution should be taken when handling wild boars or eating wild boar meat because of the possibility of human infection.

Background: The prevalence of extracorporeal cardiopulmonary resuscitation (ECPR) in patients with out-of-hospital cardiac arrest (OHCA) has been increasing rapidly worldwide. However, guidelines or clinical studies do not provide sufficient data on ECPR practice. The aim of this study was to provide real-world data on ECPR for patients with OHCA, including details of complications., Methods: We did a retrospective database analysis of observational multicenter cohort study in Japan. Adult patients with OHCA of presumed cardiac etiology who received ECPR between 2013 and 2018 were included. The primary outcome was favorable neurological outcome at hospital discharge, defined as a cerebral performance category of 1 or 2., Results: A total of 1644 patients with OHCA were included in this study. The patient age was 18-93 years (median: 60 years). Shockable rhythm in the initial cardiac rhythm at the scene was 69.4%. The median estimated low flow time was 55 min (interquartile range: 45-66 min). Favorable neurological outcome at hospital discharge was observed in 14.1% of patients, and the rate of survival to hospital discharge was 27.2%. The proportions of favorable neurological outcome at hospital discharge in terms of shockable rhythm, pulseless electrical activity, and asystole were 16.7%, 9.2%, and 3.9%, respectively. Complications were observed during ECPR in 32.7% of patients, and the most common complication was bleeding, with the rates of cannulation site bleeding and other types of hemorrhage at 16.4% and 8.5%, respectively., Conclusions: In this large cohort, data on the ECPR of 1644 patients with OHCA show that the proportion of favorable neurological outcomes at hospital discharge was 14.1%, survival rate at hospital discharge was 27.2%, and complications were observed during ECPR in 32.7%., (© 2022. The Author(s).)

Background: The novel simplified out-of-hospital cardiac arrest (sOHCA) and simplified cardiac arrest hospital prognosis (sCAHP) scores used for prognostication of hospitalised patients have not been externally validated. Therefore, this study aimed to externally validate the sOHCA and sCAHP scores in a Japanese population., Methods: We retrospectively analysed data from a prospectively maintained Japanese database (January 2012 to March 2013). We identified adult patients who had been resuscitated and hospitalised after intrinsic out-of-hospital cardiac arrest (OHCA) (n=2428, age ≥18 years). We validated the sOHCA and sCAHP scores with reference to the original scores in predicting 1-month unfavourable neurological outcomes (cerebral performance categories 3-5) based on the discrimination and calibration measures of area under the receiver operating characteristic curves (AUCs) and a Hosmer-Lemeshow goodness-of-fit test with a calibration plot, respectively., Results: In total, 1985/2484 (82%) patients had a 1-month unfavourable neurological outcome. The original OHCA, sOHCA, original cardiac arrest hospital prognosis (CAHP) and sCAHP scores were available for 855/2428 (35%), 1359/2428 (56%), 1130/2428 (47%) and 1834/2428 (76%) patients, respectively. The AUCs of simplified scores did not differ significantly from those of the original scores, whereas the AUC of the sCAHP score was significantly higher than that of the sOHCA score (0.88 vs 0.81, p<0.001). The goodness of fit was poor in the sOHCA score (ν=8, χ 2 =19.1 and Hosmer-Lemeshow test: p=0.014) but not in the sCAHP score (ν=8, χ 2 =13.5 and Hosmer-Lemeshow test: p=0.10)., Conclusion: The performances of the original and simplified OHCA and CAHP scores in predicting neurological outcomes in successfully resuscitated OHCA patients were acceptable. With the highest availability, similar discrimination and good calibration, the sCAHP score has promising potential for clinical implementation, although further validation studies to evaluate its clinical acceptance are necessary., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Heart failure in elderly people causes physical and cognitive dysfunction and often requires long-term care insurance (LTCI); however, among patients with left ventricular (LV) systolic dysfunction, the incidence and risk factors of future LTCI requirements need to be elucidated., Methods and results: The study included 1,852 patients aged ≥65 years with an echocardiographic LV ejection fraction (LVEF) ≤50%; we referred to their LTCI data and those of 113,038 community-dwelling elderly people. During a mean 1.7-year period, 332 patients newly required LTCI (incidence 10.7 per 100 person-years); the incidence was significantly higher than that for the community-dwelling people (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.32-1.64). On multivariate analysis, the risk factors at the time of echocardiography leading to future LTCI requirement were atrial fibrillation (HR, 1.588; 95% CI, 1.279-1.971), history of stroke (HR, 2.02; 95% CI, 1.583-2.576), osteoporosis (HR, 1.738; 95% CI, 1.253-2.41), dementia (HR, 2.804; 95% CI, 2.075-3.789), hypnotics (HR, 1.461; 95% CI, 1.148-1.859), and diuretics (HR, 1.417; 95% CI, 1.132-1.773); however, the LVEF was not a risk factor (HR, 0.997; 95% CI, 0.983-1.011)., Conclusions: In elderly patients with LV systolic dysfunction, the incidence of LTCI requirement was more common than that for community-dwelling people; its risk factors did not include LVEF, but included many other non-cardiac comorbidities and therapies, suggesting the need for interdisciplinary cooperation to prevent disabilities.

The prognosis of patients with connective tissue disease (CTD) has improved significantly in recent years, but interstitial lung disease (ILD) associated with connective tissue disease (CTD-ILD) remains a refractory condition, which is a leading cause of mortality. Because it is an important prognostic factor, many observational and interventional studies have been conducted to date. However, CTD is a heterogeneous group of conditions, which makes the clinical course, treatment responses, and prognosis of CTD-ILD extremely diverse. To summarize the current understanding and unsolved questions, the Japanese Respiratory Society and the Japan College of Rheumatology collaborated to publish the world's first guide focusing on CTD-ILD, based on the evidence and expert consensus of pulmonologists and rheumatologists, along with radiologists, pathologists, and dermatologists. The task force members proposed a total of 27 items, including 7 for general topics, 9 for disease-specific topics, 3 for complications, 4 for pharmacologic treatments, and 4 for non-pharmacologic therapies, with teams of 2-4 authors and reviewers for each item to prepare a consensus statement based on a systematic literature review. Subsequently, public opinions were collected from members of both societies, and a critical review was conducted by external reviewers. Finally, the task force finalized the guide upon discussion and consensus generation. This guide is expected to contribute to the standardization of CTD-ILD medical care and is also useful as a tool for promoting future research by clarifying unresolved issues., Competing Interests: Conflict of Interest Dr. Yasuhiro Kondoh received honoraria from Shionogi & Co.,Ltd. and Nippon Boehringer Ingelheim Co., Ltd. Takashi Ogura received honoraria from Shionogi & Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd.; grant support and/ or research funding from Nippon Boehringer Ingelheim Co., Ltd.; and subsidies or donations from Nippon Boehringer Ingelheim Co., Ltd. and the Mental Health Okamoto Memorial Foundation. Dr. Takafumi Suda received honoraria from AstraZeneca K.K. and Nippon Boehringer Ingelheim Co., Ltd.; grant support and/or research funding from AstraZeneca K.K. and Ono Pharmaceutical Co., Ltd.; subsidies or donations from Astellas Pharma Inc., MSD K.K., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., and Pfizer Japan Inc. Dr. Hiromi Tomioka received honoraria from Nippon Boehringer Ingelheim Co., Ltd. Dr. Hirofumi Amano received grant support and/or research funding from Sumitomo Dainippon Pharma Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd.; subsidies or donations from Actelion Pharmaceuticals Japan Ltd., Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AYUMI Pharmaceutical Corporation, Eisai Co., Ltd., MSD K.K., Taisho Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Teijin Pharma Ltd., and Bayer Yakuhin, Ltd. Dr. Masaki Anraku belongs to endowed departments sponsored by Tokio Marine & Nichido Fire Insurance Co., Ltd. Dr. Takao Fujii, received honoraria from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AbbVie GK, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Pfizer Japan Inc., Ono Pharmaciutical Cooperation Co.,Ltd., and Nippon Boehringer Ingelheim Co., Ltd., and subsidies or donations from Asahi Kasei Pharma Corporation, AbbVie GK, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, and Ono Pharmaciutical Cooperation Co., Ltd. Dr. Tomoyuki Fujisawa received grant support and/or research funding from Novartis Pharma K.K. Dr. Takahisa Gono received honoraria from Ono Pharmaceutical Co., Ltd. Dr. Masayoshi Harigai received honoraria from Chugai Pharmaceutical Co., Ltd. and subsidies or donations from Eisai Co., Ltd.; and belongs to endowed departments sponsored by AYUMI Pharmaceutical Corporation, Mitsubishi Tanabe Pharma Corporation, and Nippon Kayaku Co., Ltd. Dr. Yoshikazu Inoue received honoraria from Nippon Boehringer Ingelheim Co., Ltd. Dr. Takeshi Johkoh received honoraria from Nippon Boehringer Ingelheim Co., Ltd. Dr. Hideto Kameda received honoraria from Asahi Kasei Pharma Corporation, AbbVie GK, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K., Pfizer Japan Inc., Bristol-Myers Squibb K.K., Janssen Pharmaceutical K.K.; grant support and/or research funding from Astellas Pharma Inc., AbbVie GK, Gilead Sciences Inc., Novartis Pharma K.K., and Bristol-Myers Squibb K.K.; and subsidies or donations from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, and Chugai Pharmaceutical Co., Ltd. Dr. Kensuke Kataoka received honoraria from Nippon Boehringer Ingelheim Co., Ltd. Dr. Yasuhiro Katsumata received subsidies or donations from Mitsubishi Tanabe Pharma Corporation and Chugai Pharmaceutical Co., Ltd. Dr. Yasushi Kawaguchi received honoraria from Actelion Pharmaceuticals Japan Ltd. and Bayer Yakuhin, Ltd. Dr. Atsushi Kawakami received honoraria from Astellas Pharma Inc., AbbVie GK, Eisai Co., Ltd., MSD K.K., Ono Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., and Pfizer Japan Inc.; grant support and/or research funding from Ono Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Taisho Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., and Bristol-Myers Squibb K.K.; and subsidies or donations from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AbbVie GK, Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., and Pfizer Japan Inc. Dr. Noboru Kitamura received subsidies or donations from Ono Pharmaceutical Co., Ltd. and Chugai Pharmaceutical Co., Ltd. Dr. Kazuhiro Kurasawa received grant support and/or research funding from Pfizer Japan Inc.; and subsidies or donations from Asahi Kasei Pharma Corporation and Mitsubishi Tanabe Pharma Corporation. Dr. Yutaro Nakamura received subsidies or donations from Nippon Boehringer Ingelheim Co., Ltd. Dr. Ran Nakashima received grant support and/or research funding from Takeda Pharmaceutical Co., Ltd. Dr. Yasuhiko Nishioka, received subsidies or donations from Asahi Kasei Pharma Corporation and Pfizer Japan Inc. Dr. Masaki Okamoto received honoraria from Nippon Boehringer Ingelheim Co., Ltd. Dr. Fumikazu Sakai received honoraria from AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd., and manuscript fees from Nippon Boehringer Ingelheim Co., Ltd. Dr. Shinji Sato received subsidies or donations from Asahi Kasei Pharma Corporation, Ono Pharmaceutical Co., Ltd., and Chugai Pharmaceutical Co., Ltd. Dr. Tohru Takeuchi received honoraria from Mitsubishi Tanabe Pharma Corporation and Bristol-Myers Squibb K.K. and subsidies or donations from Asahi Kasei Pharma Corporation, Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, and Teijin Pharma Ltd. Dr. Masataka Kuwana received patent royalties and/or licensing fees from Medical & Biological Laboratories Co., Ltd.; honoraria from Actelion Pharmaceuticals Japan Ltd., Astellas Pharma Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., and Janssen Pharmaceutical K.K.; grant support and/or research funding from Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., and Bayer Yakuhin, Ltd.; and subsidies or donations from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., and Bayer Yakuhin, Ltd. Dr. Drs. Shigeki Makino, Noriyuki Enomoto, Hidenori Ichiyasu, Hideya Kitamura, Tomohiro Koga, Osamu Nishiyama, Susumu Sakamoto, Toshimasa Shimizu, Noboru Takayanagi, Reoto Takei, Tamiko Takemura, Yuko Toyoda, Hidehiro Yamada, Hideaki Yamakawa, Yasuhiko Yamano, and Yoshioki Yamasaki declare no conflicts of interest associated with this article., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Few studies have investigated the relationship between blood type and trauma outcomes according to the type of injury. We conducted a retrospective multicenter observational study in twelve emergency hospitals in Japan. Patients with isolated severe abdominal injury (abbreviated injury scale for the abdomen ≥ 3 and that for other organs < 3) that occurred between 2008 and 2018 were divided into four groups according to blood type. The association between blood type and mortality, ventilator-free days (VFD), and total transfusion volume were evaluated using univariate and multivariate regression models. A total of 920 patients were included, and were divided based on their blood type: O, 288 (31%); A, 345 (38%); B, 186 (20%); and AB, 101 (11%). Patients with type O had a higher in-hospital mortality rate than those of other blood types (22% vs. 13%, p < 0.001). This association was observed in multivariate analysis (adjusted odds ratio [95% confidence interval] = 1.48 [1.25-2.26], p = 0.012). Furthermore, type O was associated with significantly higher cause-specific mortalities, fewer VFD, and larger transfusion volumes. Blood type O was associated with significantly higher mortality and larger transfusion volumes in patients with isolated severe abdominal trauma., (© 2021. The Author(s).)

Background: Whether challenging video-assisted thoracoscopic surgery (VATS) is a minimal invasive surgery remains controversial. This study aimed to analyze causes of challenging conventional multiple-port VATS (CVATS) and conversion to thoracotomy and postoperative pain to provide indications for VATS., Methods: This was a two-center retrospective study. Challenging VATS was defined as CVATS with operation time ≥5 hours and it was converted to thoracotomy. This study included patients who were admitted to Joetsu General Hospital (Joetsu, Niigata, Japan) and Toyama University Hospital (Toyama, Japan) for elective CVATS between April 2013 and March 2019. The exclusion criteria were as follows: a planned thoracotomy, uniportal VATS, robot-assisted thoracoscopic surgery, and simultaneous resection of extrathoracic organs., Results: A total of 911 (91.6%) patients underwent CVATS. Of these cases, 876 (96.2%) were suitable VATS cases. On the contrary, 35 cases (3.8%) were recognized as challenging VATS. In 21 (2.3%) cases, VATS took ≥5 hours, and 14 (1.5%) VATS cases were converted to thoracotomy. The causes were severe adhesions (62.9%), air leak (45.7%), body position changes (22.9%), large tumor (14.3%), bronchoplasty or angioplasty (8.6%), and bleeding (2.9%). The minimum diameter of large tumors was 61.4 mm (53-67 mm). In 15 (71.4%) patients, VATS took ≥5 hours, and 10 (71.4%) patients who were converted to thoracotomy developed postoperative neuropathic pain., Conclusions: In this study, VATS ≥5 hours and conversion from VATS to thoracotomy were complicated by postoperative neuropathic pain. In case of bronchoplasty, angioplasty, and large tumor with minimum diameter ≥5 cm, a thoracotomy approach would be appropriate depending on the skill and experience of the surgeon. In cases of local or vascular sheath adhesion, if operation progress is delayed, it may be necessary to set a time limit and decide to convert to thoracotomy, considering patient's safety first.

Background: Pancreatic trauma is reportedly associated with high morbidity and mortality. Main pancreatic duct (MPD) injury is critical for treatment., Methods: As a study project of the Japanese Society for Abdominal Emergency Medicine (JSAEM), we collected the data of 163 patients with pancreatic trauma who were diagnosed and treated at JSAEM board-certified hospitals from 2006 to 2016. Clinical backgrounds, diagnostic approaches, management strategies, and outcomes were evaluated., Results: Sixty-four patients (39%) were diagnosed as having pancreatic trauma with MPD injury that resulted in 3% mortality. Blunt trauma and isolated pancreatic injury were independent factors predicting MPD injury. Nine of 11 patients with MPD injury who were initially treated nonoperatively had serious clinical sequelae and five (45%) required surgery as a secondary treatment. Among all cases, the detectability of MPD injury of endoscopic retrograde pancreatography (ERP) was superior to that of other imaging modalities (CT or MRI), with higher sensitivity and specificity (sensitivity = 0.96; specificity = 1.0)., Conclusions: Acceptable outcomes were observed in pancreatic trauma patients with MPD injury. Nonoperative management should be carefully selected for MPD injury. ERP is recommended to be performed in patients with suspected MPD injury and stable hemodynamics., (© 2020 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by John Wiley - Sons Australia, Ltd on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Two Staphylococcus aureus bacteriophages, KSAP7 and KSAP11, were isolated from sewage and characterized. Based on morphology and DNA sequences, they were assigned to the genus Silviavirus, subfamily Twortvirinae, family Herelleviridae, whose members are hypothesized to be suitable for bacteriophage therapy. The KSAP7 and KSAP11 genomes were 137,950 and 138,307 bp in size, respectively. Although their DNA sequences were almost identical, evidence of site-specific DNA rearrangements was found in two regions. Changes in the number of PIEPEK amino acid sequence repeats encoded by orf10 and the insertion/deletion of a 541-bp sequence that includes a possible tail-related gene were identified.

Background: The influence of institutional volume of out-of-hospital cardiac arrest (OHCA) cases on outcomes remains unclear., Objectives: This study evaluated the relationship between institutional volume of adult, nontraumatic OHCA cases and 1-month favorable neurologic outcomes., Methods: This study retrospectively analyzed data between January 2012 and March 2013 from a prospective observational study in the Kanto area of Japan. We analyzed adult patients with nontraumatic OHCA who underwent cardiopulmonary resuscitation by emergency medical service personnel and in whom spontaneous circulation was restored. Based on the institutional volume of OHCA cases, we divided institutions into low-, middle-, or high-volume groups. The primary and secondary outcomes were 1-month favorable neurologic outcomes and 1-month survival, respectively. A multivariate logistic regression analysis adjusted for propensity score and in-hospital variables was performed., Results: Of 2699 eligible patients, 889, 898, and 912 patients were transported to low-volume (40 institutions), middle-volume (14 institutions), and high-volume (9 institutions) centers, respectively. Using low-volume centers as the reference, transport to a middle- or high-volume center was not significantly associated with a favorable 1-month neurologic outcome (adjusted odds ratio [OR] 1.21 [95% confidence interval {CI} 0.84-1.75] and adjusted OR 0.77 [95% CI 0.53-1.12], respectively) or 1-month survival (adjusted OR 1.10 [95% CI 0.82-1.47] and adjusted OR 0.76 [95% CI 0.56-1.02], respectively)., Conclusions: Institutional volume was not significantly associated with favorable 1-month neurologic outcomes or 1-month survival in OHCA. Further investigation is needed to determine the association between hospital characteristics and outcomes in patients with OHCA., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To assess the clinical benefits of magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy for biopsy-naïve Japanese men., Methods: Between February 2017 and August 2018, 131 biopsy-naïve men who underwent targeted biopsy together with 10-core systematic biopsy at Hiroshima University Hospital were retrospectively investigated. Multiparametric magnetic resonance imaging findings were reported based on Prostate Imaging Reporting and Data System version 2., Results: The overall cancer detection rates per patient were 69.5% in systematic biopsy + targeted biopsy cores, 61.1% in systematic biopsy cores and 61.1% in targeted biopsy cores. The detection rates for clinically significant prostate cancer were 43.5% in targeted biopsy cores and 35.9% in systematic biopsy cores (P = 0.04), whereas the detection rates for clinically insignificant prostate cancer were 17.6% and 25.2% respectively (P = 0.04). Lesions in the peripheral zone were diagnosed more with clinically significant prostate cancer (54.8% vs 20.7%, P < 0.001) and International Society of Urological Pathology grade (3.2 vs 2.7, P = 0.02) than that in the inner gland. Just 4.2% (3/71) of Prostate Imaging Reporting and Data System category 2 and 3 lesions in the middle or base of the inner gland were found to have clinically significant prostate cancer. The cancer detection rate per core was 42.3% in targeted biopsy cores, whereas it was 17.9% in systematic biopsy cores (P < 0.001)., Conclusions: Targeted biopsy is able to improve the diagnostic accuracy of biopsy in detection of clinically significant prostate cancer by reducing the number of clinically insignificant prostate cancer detections compared with 10-core systematic biopsy in biopsy-naïve Japanese men. In addition, the present findings suggest that patients with Prostate Imaging Reporting and Data System category 2 or 3 lesions at the middle or base of the inner gland might avoid biopsies., (© 2019 The Japanese Urological Association.)

Background: The beneficial effect of epinephrine during resuscitation from out-of-hospital cardiac arrest (OHCA) has been inconclusive, and potential harm has been suggested, particularly in trauma victims. Although no significant improvement in neurological outcomes has been found among resuscitated patients using epinephrine, including trauma patients, the use of epinephrine is recommended in the Advanced Trauma Life Support protocol. Given that the use of vasopressors was reported to be associated with increased mortality in patients with massive bleeding, the undesirable effects of epinephrine during the resuscitation of traumatic OHCA should be elucidated. We hypothesised that resuscitation with epinephrine would increase mortality in patients with OHCA following trauma., Methods: This study is a post-hoc analysis of a prospective, multicentre, observational study on patients with OHCA between January 2012 and March 2013. We included adult patients with traumatic OHCA who were aged ≥15 years and excluded those with missing survival data. Patient data were divided into epinephrine or no-epinephrine groups based on the use of epinephrine during resuscitation at the hospital. Propensity scores were developed to estimate the probability of being assigned to the epinephrine group using multivariate logistic regression analyses adjusted for known survival predictors. The primary outcome was survival 7 days after injury, which was compared among the two groups after propensity score matching., Results: Of the 1125 adults with traumatic OHCA during the study period, 1030 patients were included in this study. Among them, 822 (79.8%) were resuscitated using epinephrine, and 1.1% (9/822) in the epinephrine group and 5.3% (11/208) in the no-epinephrine group survived 7 days after injury. The use of epinephrine was significantly associated with decreased 7-day survival (odds ratio = 0.20; 95% CI = 0.08-0.48; P < 0.01), and this result was confirmed by propensity score-matching analysis, in which 178 matched pairs were examined (adjusted odds ratio = 0.11; 95% CI = 0.01-0.85; P = 0.02)., Conclusions: The relationship between the use of epinephrine during resuscitation and decreased 7-day survival was found in patients with OHCA following trauma, and the propensity score-matched analyses validated the results. Resuscitation without epinephrine in traumatic OHCA should be further studied in a randomised controlled trial.

Aim: This study aimed to evaluate the association between myocardial abnormalities and left ventricular (LV) geometry as assessed using cardiac magnetic resonance imaging (CMRI) in systemic sclerosis (SSc) patients without cardiac symptoms., Methods: SSc patients without cardiac symptoms or cardiovascular risk factors underwent contrast CMRI. CMRI were assessed for structural and functional LV parameters and myocardial fibrosis based on myocardial late gadolinium enhancement (LGE). The correlation between brain natriuretic peptide (BNP) levels and LGE status was evaluated., Results: Among 49 patients, 27 (55%) showed LGE positivity. The most common identified LGE pattern was a linear pattern. LGE was not consistent with coronary artery distribution. There was no difference in ejection fraction between those with and without LGE. LV morphological changes were observed in 29% of SSc patients. An abnormal LV structure was detected in 44% and 14% of patients in the LGE+ and LGE- groups, respectively. The BNP levels were higher by 57% in the LGE+ group than in the LGE-group. Receiver operating characteristic analysis showed that BNP levels reliably detected myocardial abnormalities (area under the curve, 0.72; 95% confidence interval 0.58-0.88)., Conclusions: Myocardial abnormalities were common in SSc patients without cardiac symptoms. We suggest that LV morphological changes may have resulted from myocardial abnormalities. BNP may be useful as a screening tool for the detection of myocardial abnormalities in SSc patients., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Aim: To evaluate volume-outcome relationship in paediatric out-of-hospital cardiac arrest (OHCA)., Methods: This post hoc analysis of the SOS-KANTO 2012 study included data of paediatric OHCA patients <18 years old who were transported to the 53 emergency hospitals in the Kanto region of Japan between January 2012 and March 2013. Based on the paediatric OHCA case volume, the higher one-third of institutions (more than 10 paediatric OHCA cases during the study period) were defined as high-volume centres, the middle one-third institutions (6-10 cases) were defined as middle-volume centres and the lower one-third of institutions (less than 6 cases) were defined as low-volume centres. The primary outcome measurement was survival at 1 month after cardiac arrest. Multivariate logistic regression analysis for 1-month survival and paediatric OHCA case volume were performed after adjusting for multiple propensity scores. To estimate the multiple propensity score, we fitted a multinomial logistic regression model, which fell into one of the three groups as patient demographics and prehospital factors., Results: Among the eligible 282 children, 112, 82 and 88 patients were transported to the low-volume (36 institutions), middle-volume (11 institutions) and high-volume (6 institutions) centres, respectively. Transport to a high-volume centre was significantly associated with a better 1-month survival after adjusting for multiple propensity score (adjusted odds ratio, 2.55; 95% confidence interval, 1.05-6.17)., Conclusion: There may be a relationship between institutional case volume and survival outcomes in paediatric OHCA., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The oral hygiene of patients with a mental illness is an important concern in psychiatric care, and it is necessary to increase the level of self-care among these patients. In this study, we administered an oral care questionnaire to people with mental illness in Japan and compared their answers before (baseline) and at 1 week and 1, 3 and 6 months after they participated in an educational program., Methods: The questionnaire was distributed to 390 patients. It included questions about age, education, income, between-meal snacks, number of teeth, frequency of tooth brushing, and other items. The educational program was developed for the purposes of improving self-care., Results: Before the program, the proportion of male patients who had had a mental illness for ≥ 10 years was significantly higher among those patients who did not brush their teeth before bed. In addition, such patients did not have primary care dentists, and a significantly higher proportion of male patients, compared with female patients, did not undergo routine dental checkups more than once per year. The educational program resulted in an improvement in the use of fluoride toothpaste from baseline to 6 months after the intervention (p = 0.001). The daily use of interdental brushes or floss was significantly different 6 months after the intervention., Conclusions: Male and long-term inpatients need oral hygiene instructions. Our educational program showed the effects of using oral hygiene tools. Future studies should include a control group to measure the impact of the educational program.

Background: Japanese (JPN) guidelines for the management of acute pancreatitis were published in 2006. The severity assessment criteria for acute pancreatitis were later revised by the Japanese Ministry of Health, Labour and Welfare (MHLW) in 2008, leading to their publication as the JPN Guidelines 2010. Following the 2012 revision of the Atlanta Classifications of Acute Pancreatitis, in which the classifications of regional complications of pancreatitis were revised, the development of a minimally invasive method for local complications of pancreatitis spread, and emerging evidence was gathered and revised into the JPN Guidelines., Methods: A comprehensive evaluation was carried out on the evidence for epidemiology, diagnosis, severity, treatment, post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and clinical indicators, based on the concepts of the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). With the graded recommendations, where the evidence was unclear, Meta-Analysis team for JPN Guidelines 2015 conducted an additional new meta-analysis, the results of which were included in the guidelines., Results: Thirty-nine questions were prepared in 17 subject areas, for which 43 recommendations were made. The 17 subject areas were: Diagnosis, Diagnostic imaging, Etiology, Severity assessment, Transfer indication, Fluid therapy, Nasogastric tube, Pain control, Antibiotics prophylaxis, Protease inhibitor, Nutritional support, Intensive care, management of Biliary Pancreatitis, management of Abdominal Compartment Syndrome, Interventions for the local complications, Post-ERCP pancreatitis and Clinical Indicator (Pancreatitis Bundles 2015). Meta-analysis was conducted in the following four subject areas based on randomized controlled trials: (1) prophylactic antibiotics use; (2) prophylactic pancreatic stent placement for the prevention of post-ERCP pancreatitis; (3) prophylactic non-steroidal anti-inflammatory drugs (NSAIDs) for the prevention of post-ERCP pancreatitis; and (4) peritoneal lavage. Using the results of the meta-analysis, recommendations were graded to create useful information. In addition, a mobile application was developed, which made it possible to diagnose, assess severity and check pancreatitis bundles., Conclusions: The JPN Guidelines 2015 were prepared using the most up-to-date methods, and including the latest recommended medical treatments, and we are confident that this will make them easy for many clinicians to use, and will provide a useful tool in the decision-making process for the treatment of patients, and optimal medical support. The free mobile application and calculator for the JPN Guidelines 2015 is available via http://www.jshbps.jp/en/guideline/jpn-guideline2015.html., (© 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Merkel cell carcinoma is a rare and aggressive neuroendocrine-derived skin cancer arising most commonly on the sun-exposed head and neck skin of elderly and immunocompromised patients. Although a combination of wide excision and adjuvant radiotherapy is the optimal therapeutic approach for Merkel cell carcinoma, radiation monotherapy has recently been recommended for unresectable tumors. We report here a case of Merkel cell carcinoma treated with radiation monotherapy and reviewed Merkel cell carcinoma cases treated with radiotherapy alone in Japan. A 75-year-old man was referred for treatment of a tumor on the upper lip with a swollen submental lymph node. The histopathological diagnosis from biopsied material was Merkel cell carcinoma (T3N1bM0, stage IIIB). The submental lymph node was extirpated and radiation monotherapy was applied according to the 2014 National Comprehensive Cancer Network Guidelines because the Eastern Cooperative Oncology Group Performance Status of the patient was grade 3 and the patient and his family did not desire surgery. The primary site and bilateral upper neck regions were irradiated with 45 Gy followed by 20 Gy irradiation for the primary site alone. Three months after radiotherapy, the tumor seemed to have completely remitted. Approximately 1 year after radiotherapy, no evidence of local recurrence or late metastasis has been noted. Radiation monotherapy should be considered as a curative treatment for Merkel cell carcinoma, particularly in situations where extensive surgery is not favored.

Objective: Autophagy is the regulated catabolic process for recycling damaged or unnecessary organelles, which plays crucial roles in cell survival during nutrient deficiency, and innate immune defense against pathogenic microorganisms. Autophagy has been also reported to be involved in various conditions including inflammatory diseases. IRGM (human immunity-related GTPase) has an important function in eliminating Mycobacterium tuberculosis from host cells via autophagy. We examined the association between genetic polymorphism and clinical course/outcome in severely septic patients., Methods: The study included 125 patients with severe sepsis/septic shock (SS) and 104 non-sepsis patients who were admitted to the intensive care unit (ICU) of Chiba University Hospital between October 2001 and September 2008 (discovery cohort) and 268 SS patients and 454 non-sepsis patients who were admitted to ICUs of five Japanese institutions including Chiba University Hospital between October 2008 and September 2012 (multi-center validation cohort). Three hundred forty seven healthy volunteers who consented to this study were also included. Genotyping was performed for a single-nucleotide polymorphism (SNP) within the coding region of IRGM, IRGM(+313) (rs10065172). Lipopolysaccharide challenge of whole blood from randomly selected healthy volunteers (n = 70) was performed for comparison of IRGM mRNA expression among different genotypes., Results: No significant difference in genotypic distributions (CC/CT/TT) at the IRGM(+313) locus was observed among the three subject groups (SS, non-sepsis, and healthy volunteers) in either cohort. When mortality were compared, no significant difference was observed in the non-sepsis group, while TT homozygotes exhibited a significantly higher mortality than the CC+CT genotype category in the SS group for both cohorts (P = 0.043, 0.037). Lipopolysaccharide challenge to whole blood showed a significant suppression of IRGM mRNA expression in TT compared with the CC+CT genotype category (P = 0.019)., Conclusions: The data suggest that the IRGM(+313), an autophagy-related polymorphic locus, influences outcome in severely septic patients, with the possible involvement of autophagy in sepsis exacerbation.

Rare non-synonymous variants of TREM2 have recently been shown to be associated with Alzheimer's disease (AD) in Caucasians. We here conducted a replication study using a well-characterized Japanese sample set, comprising 2,190 late-onset AD (LOAD) cases and 2,498 controls. We genotyped 10 non-synonymous variants (Q33X, Y38C, R47H, T66M, N68K, D87N, T96K, R98W, H157Y, and L211P) of TREM2 reported by Guerreiro et al. (2013) by means of the TaqMan and dideoxy sequencing methods. Only three variants, R47H, H157Y, and L211P, were polymorphic (range of minor allele frequency [MAF], 0.0002-0.0059); however, no significant association with LOAD was observed in these variants. Considering low MAF of variants examined and our study sample size, further genetic analysis with a larger sample set is needed to firmly evaluate whether or not TREM2 is associated with LOAD in Japanese.

Introduction: The incidence of preventable trauma death in the current Japanese emergency medical system remains high. The present study aimed to determine rates of clearly preventable and possibly preventable trauma deaths due to traffic accidents in Chiba Prefecture, Japan, and to consider associated problems and solutions., Materials and Methods: During 2011, 175 victims died after traffic accidents in Chiba Prefecture. Of these, the deaths of 69 persons who had vital signs at the time of emergency medical service contact were classified as clearly preventable, possibly preventable, or not preventable through the peer review discussion. We also examined problems associated with deaths that were clearly preventable or possibly preventable., Results: Of the 69 deaths, 9 (13%) were classified as clearly preventable, 11 (16%) as possibly preventable, and 49 (71%) as not preventable. Of the 20 clearly or possibly preventable deaths (each death potentially comprising multiple problems), 5 were related to selection of the hospital before hospital arrival, 4 to problems with regional emergency medical systems, and 15 to inappropriate hemodynamic management, including transfusion and delayed (or not attempted) hemostasis in the hospital., Discussion: Problems of these 20 deaths showed that appropriate triage at the scene, centralization of patients with severe trauma, and trauma centers are necessary in Japan. Under-triage before arrival at the hospital was related to clearly and possibly preventable deaths. Upgrading the triage category for victims with torso injury must be considered. Not all emergency critical care centers in Japan are able to provide severe trauma care. Preventable trauma deaths occur even in some emergency critical care centers; therefore, we need centralization of severe trauma patients from wider area to reduce the incidence of preventable trauma death.

Aims: In order for hospitals to work efficiently in a pandemic, it is important to know how a pandemic affects the hospital staff. The aim of the present study was to investigate the psychological impact of the pandemic (H1N1) 2009 on hospital workers and how it was affected by the characteristics of the hospital, gender, age, job and work environment., Methods: In late June 2009, soon after the pandemic had ended in Kobe city, Japan, a questionnaire was distributed consisting of questions on sociodemographic characteristics, 19 stress-related questions and the Impact of Event Scale (IES) to all 3635 employees at three core general hospitals in Kobe. Exploratory factor analysis was applied to the 19 stress-related questions, and this produced four factors for evaluation (anxiety about infection, exhaustion, workload, and feeling of being protected). Multiple regression models were used to evaluate the association of personal characteristics with each score of the four factors and the IES., Results: Valid answers were received from 1625 employees. Workers at a hospital with intense liaison psychiatric services felt less psychological impact. Workers at a hospital that provided staff with information about the pandemic less frequently, felt unprotected. Workers in work environments that had a high risk of infection felt more anxious and more exhausted. The total IES score was higher in workers in high-risk work environments., Conclusions: It is important for hospitals to protect hospital workers during a pandemic and to rapidly share information about the pandemic. Liaison psychiatric services can help to reduce the impact of the pandemic on hospital workers., (© 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.)

Background: The professionalism of hospital workers in Japan was challenged by the pandemic (H1N1) 2009. To maintain hospital function under critical situations such as a pandemic, it is important to understand the factors that increase and decrease the willingness to work. Previous hospital-based studies have examined this question using hypothetical events, but so far it has not been examined in an actual pandemic. Here, we surveyed the factors that influenced the motivation and hesitation of hospital workers to work in Japan soon after the pandemic (H1N1) 2009., Methods: Self-administered anonymous questionnaires about demographic character and stress factors were distributed to all 3635 employees at three core hospitals in Kobe city, Japan and were collected from June to July, 2009, about one month after the pandemic (H1N1) in Japan., Results: Of a total of 3635 questionnaires distributed, 1693 (46.7%) valid questionnaires were received. 28.4% (N = 481) of workers had strong motivation and 14.7% (N = 249) had strong hesitation to work. Demographic characters and stress-related questions were categorised into four types according to the odds ratios (OR) of motivation and hesitation to work: some factors increased motivation and lowered hesitation; others increased motivation only; others increased hesitation only and others increased both motivation and hesitation. The strong feeling of being supported by the national and local governments (Multivariate OR: motivation; 3.5; CI 2.2-5.4, hesitation; 0.2; CI 0.1-0.6) and being protected by hospital (Multivariate OR: motivation; 2.8; CI 2.2-3.7, hesitation; 0.5; CI 0.3-0.7) were related to higher motivation and lower hesitation. Here, protection included taking precautions to prevent illness among workers and their families, providing for the care of those who do become ill, reducing malpractice threats, and financial support for families of workers who die on duty. But 94.1% of the respondents answered protection by the national and local government was weak and 79.7% answered protection by the hospital was weak., Conclusions: Some factors have conflicting effects because they increase both motivation and hesitation. Giving workers the feeling that they are being protected by the national and local government and hospital is especially valuable because it increases their motivation and lowers their hesitation to work.

Objective: The objective of this study was to assess the influence of factors of obesity and craniofacial morphology on the degree of obstructive sleep apnea syndrome (OSAS) in Japanese individuals., Study Design: The subjects were 138 adult male patients who visited the Clinic for Snoring & Obstructive Sleep Apnea at Niigata University Medical and Dental Hospital with chief complaints of snoring and apnea. Standardized lateral cephalograms were taken at the first visit, and overnight polysomnography was carried out for evaluation of each subject before treatment., Results: Univariate and multivariate analyses were performed to investigate factors affecting the severity of OSAS. These analyses showed that obesity, skeletal conditions such as short mandibular body and mandibular retreat, size of the tongue and position of the hyoid bone, and shape of the airway were associated with the severity of OSAS., Conclusion: In Japanese male OSAS patients, skeletal abnormalities are thought to be the factors that most greatly affect severity of OSAS.

Regulators of G-protein signaling are a family of proteins that negatively regulate the intracellular signaling of G protein-coupled receptors, such as the serotonin receptor. Recent studies have suggested that one of these proteins, the regulator of G-protein signaling 2 (RGS2), plays an important part in anxiety and/or aggressive behavior. To explore the involvement of the RGS2 gene in the vulnerability to suicide, we screened Japanese suicide victims for sequence variations in the RGS2 gene and carried out an association study of RGS2 gene polymorphisms with suicide victims. In the eight identified polymorphisms that were identified by mutation screening, we genotyped four common single-nucleotide polymorphisms (SNPs) in the RGS2 gene, and found significant differences in the distribution of the SNP3 (C+2971G, rs4606) genotypes and alleles of the SNP2 (C-395G, rs2746072) and the SNP3 between completed suicides and the controls. The distribution of the haplotype was also significantly different between the two groups (global p<0.0001). Furthermore, RGS2 immunoreactivity significantly increased in the amygdala and the prefrontal cortex (Brodmann area 9 (BA9)) of the postmortem brain of the suicide subjects. These findings suggest that RGS2 is genetically involved in the biological susceptibility to suicide in the Japanese population.

Genetic factors have been suggested to be involved in suicide. Although some genetic factors, such as serotonergic transduction, have been associated with suicide, the results are inconsistent. There is a possibility that various signaling anomalies are involved in the biological vulnerability to suicide. We carried out a genome-wide gene-expression study in the brains of suicide victims using DNA microarrays;14-3-3 epsilon, which is related to neurogenesis, was one of the genes upregulated in the brains of suicide victims in the microarray analysis. This was confirmed by Western blot analysis. To examine the possibility of the involvement of 14-3-3 epsilon in the pathogenesis of suicide, we investigated the association of the 14-3-3 epsilon gene and completed suicide. We used three high-frequency SNPs (rs1532976, rs3752826, and rs9393) and found a significant association of two alleles (rs1532976 and rs3752826) with completed suicide (p < 0.05). Moreover, the distribution of haplotype revealed a more significant difference between completed suicide and controls (p=0.0005). This finding suggests that 14-3-3 epsilon is a potential suicide susceptibility gene and implies that dysregulation of neurogenesis may be involved in suicide.

The Japanese Board of General Surgery as well as the Japanese Board of Thoracic Surgery voted to change the educational and training requirements for certification eligibility. The health care system has been modified due to a reduction of the budget for national health care, such as introduction of Diagnosis Related Groups (DRG)/Prospective Payment System (PPS). Several problems regarding the system have already been discussed in the United States, ranging from 30-year experience of residency program to 20-year experience of health care system. In a residency requirement, training period became longer in Japan than in the United States, although number of cases required is ten times less in Japan. The General Surgery Board now became mandatory in Japan, whereas optional in the United States. Interprogram transfer is possible in the United States, but not in Japan. Quality control has been organized for Thoracic Surgery in the United States, but the Japanese counterpart needs more work. In health care system, health insurance is mandatory and operated publicly in Japan while the United States counterpart is mostly optional and managed privately. Malpractice suits are 7-8 times more frequent in the United States. DRG/PPS health care system was temporarily useful in reducing the national budget for health care in the United States. However, an incentive to treat patients with uncomplicated diseases and short hospital stay increased the expenditure. In order to control this, Peer Review Organization has been established and restricted the physician's activities. Because health insurance is optional in the United States, people opt for cheaper health insurance with greater benefits. So the health insurance companies with huge number of customers have had strong opinions over physicians and hospitals. This also has created restrictions on practice. These potential problems may occur shortly in the Japanese residency program and health care system as well. Thus, preventive strategies may be needed.

From October 2001 to September 2002, we collected the specimen from 370 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of the isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 458 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 456 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 69, Streptococcus pneumoniae 72, Haemophilus influenzae 85, Pseudomonas aeruginosa (non-mucoid) 44, P. aeruginosa (mucoid) 13, Klebsiella pneumoniae 32, Moraxella subgenus Branhamella catarrhalis 32, and others. Of 69 S. aureus strains, those with 4 micrograms/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 43.5%. Vancomycin and arbekacin showed the most potent activities against MRSA as observed in 2000. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) was 59.7% and both rates of PISP and PRSP were the highest after 1992. Carbapenems had strong activities against S. pneumoniae. Especially, panipenem and imipenem inhibited the growth of all 72 strains at 0.125 and 0.5 microgram/mL, respectively. Generally, all drugs had strong activities against H. influenzae with MIC90s of 16 micrograms/mL or less. The drug that had the strongest activity against H. influenzae was levofloxacin, which inhibited the growth of 80 of the 85 strains at 0.063 microgram/mL. Against P. aeruginosa mucoid strain, meropenem had a strong activity with MIC90 of 0.5 microgram/mL while, against non-mucoid strain, tobramycin had a strong activity with MIC90 of 2 micrograms/mL. K. pneumoniae showed good susceptibilities to all drugs except ampicillin and minocycline, and the MIC90s were 4 micrograms/mL or less. Particularly, cefmenoxime, cefpirome, and imipenem had the strongest activity (MIC90: 0.125 microgram/mL), and cefozopran had a strong activity, inhibiting the growth of all strains at 0.25 microgram/mL. Also, all drugs generally had strong activities against M. (B.) catarrhalis. MIC90s of all drugs were 4 micrograms/mL or less. The drug that had the strongest activity was minocycline and levofloxacin inhibiting all 32 strains at 0.063 microgram/mL. Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (40.5%). As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 39.2% and 37.3% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (19.3%) and S. pneumoniae (19.9%). In contrast, H. influenzae (22.0%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (20.8%) and H. influenzae (21.5%). S. pneumoniae and H. influenzae decreased after the initiation of drug administration while S. aureus increased. The isolation frequency of P. aeruginosa was higher after than before the initiation of drug administration. The bacteria were frequently isolated from the patients who had already treated with cephems were S. aureus and P. aeruginosa. From the patients who had already treated with macrolides, S. pneumoniae was the most frequently isolated while S. aureus was the most frequently isolated from the patients pre-treated with quinolones.

The trauma care system in Japan was set up in the 1960s in response to social problems caused by traffic accidents and has since been altered extensively. First-aid and patient transfer are performed by emergency personnel belonging to a fire station. Instead of 'western-style trauma centres', three types of facilities exist: (1) primary emergency care facilities for treating mild cases not requiring hospitalisation; (2) secondary emergency hospitals directed to treating moderately severe disease or injury; (3) tertiary emergency hospitals corresponding to the emergency departments of university hospitals, or lifesaving emergency centres, able to manage the most severe cases such as myocardial infarction, cerebrovascular accident and polytrauma. Although the quantity of emergency facilities and hospitals appears sufficient, the quality of emergency care needs to be improved. This could be accomplished by the unification of small hospitals to create larger hospitals, and/or by the establishment of trauma centres, as well as by improvements in relevant education and training.

Objective: To evaluate the usefulness of cellular injury score (CIS) and Sepsis-related Organ Failure Assessment (SOFA) score for determination of the severity of multiple organ dysfunction syndrome (MODS)., Design: A prospective observational study., Setting: A medical and surgical intensive care unit (ICU) of a teaching hospital., Patients: Forty-seven consecutive MODS patients., Measurements and Results: SOFA score and CIS were measured every day for 12 months for 47 MODS patients. Comparison was made of the SOFA score and CIS for usefulness in the scoring of severity of MODS in 26 survivors and 21 non-survivors. In addition, receiver operating characteristics (ROC) analysis was used to determine the usefulness of these two indexes as predictors of prognosis. No significant differences were found on admission between the survivors and non-survivors, but significant differences between the two subgroups (p < 0.001) were found in maximum value within 1 week after admission and maximum value during the course of treatment for both indexes. Analysis of changes after admission indicated that significant differences between survivors and non-survivors began to appear on day 3 of admission for both indexes; at that time SOFA score began to deteriorate in the non-survivors while CIS began to improve in the survivors. ROC analysis demonstrated that the area under the ROC curve was 0.769 for SOFA scores and 0.760 for CIS., Conclusions: Both SOFA score and CIS sequentially reflected the severity of MODS. Furthermore, they were comparable in diagnostic value as predictors of prognosis. These findings may indicate the possibility that MODS is a summation of effects of cellular injury. In addition, sequential evaluation of both SOFA score and CIS would provide a more accurate prediction of prognosis than conventional methods.

Adenovirus strains of a new type were isolated from patients with epidemic keratoconjunctivitis. They were not completely neutralized by any antiserum against adenovirus prototypes. PCR followed by restriction endonuclease analysis demonstrated that they were type 8. PCR followed by sequencing revealed a high homology rate between them and type 9.

To clarify the features of the seminiferous epithelium of the Japanese rat snake, Elaphe climacophora, the identification of spermatogonium and the examination of features of cell to cell junctions were performed in the present study. As for the identification, 5-bromo-2-deoxyuridine (BrdU) incorporation was examined immunohistochemically to mark spermatogonia. The seminiferous epithelium was observed throughout a year at the electron microscopic level. BrdU immunoreactivity was detected not only in the cells of the first layer of the seminiferous epithelium but also in the second and/or third layers. The cells immunoreactive in the first layer did not seem to attach to the basement membrane and were recognized throughout a year. To investigate cell to cell junctions, we performed actin filament detection by phalloidin staining. Distribution of actin filaments was different from that in mammalian species. At the ultrastructural level, Sertoli-Sertoli cell junctions were observed. Sertoli cells formed junctional complexes. Tight junctions were clearly found, but lacked the backing by actin filaments. These results indicate that the blood-testis barrier of the Japanese rat snake was structurally different from that of mammalian species. In conclusion, the seminiferous epithelium of the Japanese rat snake is intermediate in morphology between amphibians and mammals.

Bacteria isolated from lower respiratory tract infections were collected in cooperation with institutions located throughout Japan, since 1981. IKEMOTO et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In 23 institutions around the entire Japan, 492 strains of presumably etiological bacteria were isolated mainly from the sputum of 421 patients with lower respiratory tract infections from October 1994 to September 1995. MICs of various antibacterial agents and antibiotics were determined against 70 strains of Staphylococcus aureus, 101 strains of Streptococcus pneumoniae, 92 strains of Haemophilus influenzae, 61 strains of Pseudomonas aeruginosa (non-mucoid strains), 25 strains of Pseudomonas aeruginosa (mucoid strains), 48 strains of Moraxella subgenus Branhamella catarrhalis, 14 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were assessed except for those strains that died during transportation. 1. S. aureus. S. aureus strains for which MICs of oxacillin were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 51.4%, but the frequency of the drug resistant bacteria decreased comparing to the previous year's 56.0%. Vancomycin showed the highest activity against S. aureus with MIC80 of 0.5 microgram/ml. 2. S. pneumoniae. Most of the drugs tested showed potent activities against S. pneumoniae. Imipenem of carbapenems showed the most potent activity with MIC80 was 0.063 microgram/ml. Erythromycin and clindamycin showed low activities with MIC80s > or = 256 micrograms/ml. Among these strains, however, 46.5% and 68.3% of strains, were quite sensitive toward these agents, respectively, with MICs of 0.063 microgram/ml. 3. H. influenzae. The activities of all drugs were potent against H. influenzae tested. Cefmenoxime a cephem, showed the most potent activity, the MICs of this drug against all of the 92 strains were 0.063 microgram/ml. Ofloxacin also showed a potent activity, and inhibited about 96% of strains with MIC of 0.063 microgram/ml. 4. P. aeruginosa (mucoid strains). Tobramycin showed the most potent activity against P. aeruginosa (mucoid strains) with MIC80 of 0.5 microgram/ml. Gentamicin, arbekacin and ciprofloxacin showed next potent activities, and their MIC80s were 2 micrograms/ml. 5. P. aeruginosa (non-mucoid strains). Tobramycin showed the most potent activity against P. aeruginosa (non-mucoid strains) with MIC80 of 2 micrograms/ml. Comparing to the activities against P. aeruginosa (mucoid strains), the activities of all the drugs tested were lower against P. aeruginosa (non-mucoid strains). 6. K. pneumoniae. Carumonam showed the most potent activity against K. pneumoniae with MIC80 of 0.063 microgram/ml. Cefozopran showed the next most potent activity with MIC80 of 0.125 microgram/ml. Ampicillin and cephems except cefpodoxime, cefozopran and cefditoren showed low activities and their MIC80s were > or = 16 micrograms/ml, and their MICs were all higher than > or = 4 micrograms/ml. 7. M. (B.) catarrhalis. Imipenem and ofloxacin showed the most potent activities against M. (B.) catarrhalis, their MIC80s were 0.063 microgram/ml. Erythromycin and minocycline showed the next highest activities with their MIC80s at 0.25 microgram/ml. Also, we investigated year to year changes in the background of patients, the respiratory infectious diseases, and the etiology of bacteria. Patients characteristics, in this period of investigation showed varieties of infectious diseases found in patients in a high age bracket, and the patients over age 60 accounted for 62.0% of all the cases. Different lower respiratory tract infectious were distributed as follows: chronic bronchitis and bacterial pneumonia accounted for the greatest number of cases with 35.6%, 27.1%, respectively, followed by

A 28-year old female patient with virilization due to left adrenocortical adenoma was studied. The patient had clinical features of hyperandrogenism such as hirsutism and a low pitched voice, but not of hypercorticoidism. Plasma testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were high. Although the basal plasma cortisol concentration and urinary excretion of 17-hydroxycorticosteroids (17-OHCS) were within the normal range, the absence of diurnal variation in plasma cortisol and loss of suppressibility by dexamethasone suggested constitutive secretion of cortisol by the tumor. Inappropriate cortisol secretion was also supported by blunted ACTH response to provocative stimuli. After successful removal of the left adrenal tumor, such endocrinological abnormalities were all normalized. Immunohistochemical analysis revealed that tumor cells were positively stained for C21 hydroxylase cytochrome P-450 (P-450C21) and P-450(11) beta which convert 17-hydroxy (OH) progesterone to cortisol as well as P-450SCC, 3 beta-hydroxysteroid dehydrogenase and P-450(17) alpha which are involved in testosterone biosynthesis. These findings suggest that adrenocortical adenoma secretes predominantly testosterone and constitutively cortisol in a young woman patient with virilization.

Forty-nine artificial cardiac valves implanted in 44 patients less than 15 years old were reviewed. Out of 49 valves, 16 were mechanical and 33 were xenografts. Average follow-up was 2 years 5 months. Marked valvular stenosis developed in 11 out of the 33 xenografts, an incidence of 15% per patient-year. In patients with a xenograft valve, the incidence of sepsis was found to be 4% per patient-year and brain accidents, 4% per patient-year. In patients with mechanical valves, the incidence of stenosis was only 2% per patient-year and brain accidents, 2% per patient-year. There was no sepsis. From these follow-up results, mechanical valves seem to be superior to xenografts when used in patients less than 15 years old.