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Ventricular assist device (VAD) infections are frequent causes of hospital readmission. The risk factors and optimal preventive strategies for such, including chronic suppressive antibiotics (CSA), remain uncertain. We performed a single-center, retrospective, observational cohort study assessing continuous flow VAD recipients who underwent implantation between 2008 and 2018 in Japan. From primary VAD infection (VADI), we followed the patients for recurrent infection, defined as relapsing VAD-specific (e.g., localized infections) or VAD-related (e.g., bacteremia) infections requiring hospital readmission. CSA was defined as the use of oral antimicrobial agents continued beyond initial antibiotic use until transplantation, VAD withdrawal, VADI recurrence, or death. Survival analysis was performed to identify risk factors for recurrent infection accounting for competing risks (e.g., deaths and transplants). Among 163 eligible patients, 76 patients had VADIs. The main causative organism in primary VADI was Staphylococcus aureus (63%, 48/76). Among them, 41 had recurrent infections, whereas 35 had none during the follow-up period (median, 335 days). Thirty-six patients received CSA for a median of 478 days. Although CSA was associated with a decreased risk of recurrent infection [adjusted sub-distribution hazard ratio (SHR), 0.40; 95% confidence interval (CI), 0.18-0.89; P = 0.03], this protective effect was observed only after primary VAD-specific infection (SHR, 0.28; 95% CI, 0.12-0.64; P < 0.01) but not after VAD-related infection. Surgical procedures during primary VADI were associated with an increased risk (SHR, 2.00; 95% CI, 1.10-3.66; P = 0.02). One patient had an adverse drug reaction. CSA may be an effective approach to limit relapsing VADIs following a primary VAD-specific infection with minimal adverse events., Importance: Ventricular assist device infections (VADIs) are a significant complication leading to hospital readmissions. However, the risk factors and optimal preventive strategies for VADI remain unclear. This study investigated the effectiveness of chronic suppressive antibiotic therapy in patients with VADI. We found that the use of chronic suppressive antibiotic therapy was associated with a reduction in the risk of VADI recurrence with few adverse reactions. Our findings suggest the potential benefit of chronic suppressive antibiotics in preventing infections in selected cases. Our findings are relevant for the management of patients with ventricular assist devices awaiting heart transplantation, providing valuable insights for clinical practice., Competing Interests: H.K. reports receiving consultation fees from Mitsubishi-Tanabe Pharma Corporation, and EPS Corporation, and a speaker fee from Chugai Pharmaceutical Co., Ltd. He is affiliated with the Department of Health Quality Assessment at the University of Tokyo, a social collaboration department supported by the National Clinical Database, Johnson & Johnson K.K., Nipro Corporation, and Intuitive Surgical Sàrl. S.H. has received grants or contracts from Shinogi & Company Ltd., and received payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational activities from Shinogi & Co., Ltd., MSD, Daiichi Sankyo, and Nissui Pharmaceutical. No other competing financial interests declared.

Purpose: This prospective cohort study examined the effects of the number of present and functional teeth on mortality among older Japanese adults requiring nursing care in an environment of comprehensive oral hygiene and nutritional management., Methods: The study included 174 older adults (mean age: 84.4 ± 8.3 years; male/female: 49/125) in need of support or long-term care, who resided in either a local specialized healthcare facility or their own homes, and received daily oral hygiene and nutritional support at facilities in Okayama, Japan. The initial clinical oral examination along with assessment of general physical condition and nursing environment of the participants were performed in July 2013 and followed up for one year., Results: All-cause mortality occurred in 28 (mean age: 88.7 ±13.4 years; male/female: 6 /22) individuals during the follow-up period. Cox proportional hazard analysis indicated that older age, low performance in activities of daily living (Barthel Index <40), and underweight status (body mass index <18.5) were significant risk factors for mortality. The number of present and functional teeth were not found to be significant risk factors for mortality., Conclusions: During the one-year follow-up period, the number of present and functional teeth did not have a significant impact on mortality among older Japanese adults requiring nursing care in a well-managed environment of oral hygiene and nutritional status.

In April 2021, destination therapy (DT) was finally approved in Japan. Since DT does not aim at heart transplantation (HT), our goal is to have a patient safely remain on an implantable ventricular assist device (VAD) for the rest of his/her life. To achieve this goal, similarly to bridge-to-transplant (BTT) patients, the authors believe the following six aspects are even more crucial in DT patients: (1) to appropriately assess risks before implantation, (2) to carefully determine the ability to manage the device by multidisciplinary discussions, (3) to prevent complications by improving the quality of care, (4) to expand the number of facilities that can take care of DT patients by improving collaboration among the facilities, (5) to reduce the burden of caregivers by utilizing social resources, and (6) to establish a home palliative care system based on advance care planning. In addition, for elderly DT patients to live happy and long lives, it is essential to help them to find a purpose of life and to keep activities of daily living, such as employment, schooling, and participation in social activities, just like the general elderly population. Our goals are not only to do our best for the patients just in front of us, but also to establish a system to follow up our DT cohort, same as BTT one, by all-Japan manner. In the present review, we discuss the current state of DT in Japan and what we need to focus on to maintain or improve its long-term performance., (© 2024. The Author(s).)

Aim: To clarify the diagnostic process of the causative disease of abnormal uterine bleeding (AUB) in Japan according to the International Federation of Gynecology and Obstetrics AUB diagnostic system., Methods: Patients diagnosed with AUB were included in a nationwide survey of AUB conducted during any 2-week period between December 2019 and January 2020. The second survey included information on patient background, AUB symptoms, examinations for diagnosing AUB, the order in which they were performed, and the causative diseases of AUB., Results: Correspondence analysis showed an association between hormonal testing, hysterosalpingography, and magnetic resonance imaging (MRI) in patients with amenorrhea, and heavy menstrual bleeding was strongly correlated with various examinations, such as coagulation tests, pelvic MRI, and endometrial cytology or biopsy. The results also indicated that each AUB causative disease can be diagnosed based on a specific examination profile., Conclusion: We clarified the process of diagnosing the causative disease of AUB in our country and determined that it was mainly diagnosed by imaging and pathological examination in cases of structural disease. The high rate of AUB-E and the low rate of AUB-C are possibly associated with specific examination trends in Japan. The results of this study will be useful for the development of a standard protocol for AUB diagnosis in our country., (© 2024 The Author(s). Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Background: ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock (STEMI-CS) is associated with high mortality rates. Patients admitted during off-hours, specifically on weekends and at night, show higher mortality rates, which is called the "off-hours effect". The off-hours effect in patients with STEMI-CS treated with mechanical circulatory support, especially Impella, has not been fully evaluated., Aims: We aimed to investigate whether off-hours admissions were associated with higher mortality rates in this population., Methods: We used large-scale Japanese registry data for consecutive patients treated with Impella between February 2020 and December 2021 and compared on- and off-hours admissions. On- and off-hours were defined as the time between 8:00 and 19:59 on weekdays and the remaining time, respectively. The Cox proportional hazards model was used to calculate the adjusted hazard ratios (aHRs) for 30-day mortality., Results: Of the 1,207 STEMI patients, 566 (46.9%) patients (mean age: 69 years; 107 females) with STEMI-CS treated with Impella were included. Of these, 300 (53.0%) were admitted during on-hours. During the follow-up period (median 22 days [interquartile range 13-38 days]), 112 (42.1%) and 91 (30.3%) deaths were observed among patients admitted during off- and on-hours, respectively. Off-hours admissions were independently associated with a higher risk of 30-day mortality than on-hours admissions (aHR 1.60, 95% confidence interval: 1.07-2.39; p=0.02)., Conclusions: Our findings indicated the persistence of the "off-hours effect" in STEMI-CS patients treated with Impella. Healthcare professionals should continue to address the disparities in cardiovascular care by improving the timely provision of evidence-based treatments and enhancing off-hours medical services.

Background: Adolescents and young adults (AYAs) represent a small proportion of patients with cancer. The genomic profiles of AYA patients with cancer are not well-studied, and outcomes of genome-matched therapies remain largely unknown., Patients and Methods: We investigated differences between Japanese AYA and older adult (OA) patients in genomic alterations, therapeutic evidence levels, and genome-matched therapy usage by cancer type. We also assessed treatment outcomes., Results: AYA patients accounted for 8.3% of 876 cases. Microsatellite instability-high and/or tumor mutation burden was less common in AYA patients (1.4% versus 7.7% in OA; P = 0.05). However, BRCA1 alterations were more common in AYA patients with breast cancer (27.3% versus 1.7% in OA; P = 0.01), as were MYC alterations in AYA patients with colorectal cancer (23.5% versus 5.8% in OA; P = 0.02) and sarcoma (31.3% versus 3.4% in OA; P = 0.01). Genome-matched therapy use was similar between groups, with overall survival tending to improve in both. However, in AYA patients, the small number of patients prevented statistical significance. Comprehensive genomic profiling-guided genome-matched therapy yielded encouraging results, with progression-free survival of 9.0 months in AYA versus 3.7 months in OA patients (P = 0.59)., Conclusion: Our study suggests that tailored therapeutic approaches can benefit cancer patients regardless of age., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The volume of surgical services has significantly reduced globally due to the coronavirus disease 2019 (COVID-19) pandemic. This study evaluated the level of recovery in terms of the number of operations performed in Japan in 2021, based on nationwide periodic surveillance., Methods: Information on the weekly and annual volumes of 20 representative procedures in 6 surgical subspecialties in 2021 was extracted from the National Clinical Database. Statistical data for 2018 and 2019 (pre-pandemic era) were compared with those for 2020. Data on waves of infection, peak period, and high-prevalence areas (13 of 47 prefectures) were analyzed individually., Results: The volumes of the 10 procedures, including gastrectomy, hepatectomy, valve replacement and valve plasty, coronary artery bypass grafting, infrarenal abdominal aorta replacement, ventricular septal defect closure, lung lobectomy, inguinal hernia repair (age < 16 years old), and appendectomy (age < 16 years old), did not reach 95% of that in the pre-pandemic era. The most striking decline in the surgical volume of these 10 procedures was observed during the peak period of wave 5 in high-prevalence areas., Conclusion: This near-complete enumeration survey identified the polarization of 20 representative procedures in terms of resumption of surgical service after the pandemic., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Aims: A multi-stakeholder consensus has proposed MASLD (metabolic dysfunction-associated steatotic liver disease). We aimed to investigate the pathological findings related to the mid-term mortality of patients with biopsy-proven MASLD in Japan., Methods: We enrolled 1349 patients with biopsy-proven MASLD. The observational period was 8010 person years. We evaluated independent factors associated with mortality in patients with MASLD by Cox regression analysis. We also investigated pathological profiles related to mortality in patients with MASLD using data-mining analysis., Results: The prevalence of MASH and stage 3/4 fibrosis was observed in 65.6% and 17.4%, respectively. Forty-five patients with MASLD died. Of these, liver-related events were the most common cause at 40% (n = 18), followed by extrahepatic malignancies at 26.7% (n = 12). Grade 2/3 lobular inflammation and stage 3/4 fibrosis had a 1.9-fold and 1.8-fold risk of mortality, respectively. In the decision-tree analysis, the profiles with the worst prognosis were characterised by Grade 2/3 hepatic inflammation, along with advanced ballooning (grade 1/2) and fibrosis (stage 3/4). This profile showed a mortality at 8.3%. Furthermore, the random forest analysis identified that hepatic fibrosis and inflammation were the first and second responsible factors for the mid-term prognosis of patients with MASLD., Conclusions: In patients with biopsy-proven MASLD, the prevalence of MASH and advanced fibrosis was approximately 65% and 20%, respectively. The leading cause of mortality was liver-related events. Hepatic inflammation and fibrosis were significant factors influencing mid-term mortality. These findings highlight the importance of targeting inflammation and fibrosis in the management of patients with MASLD., (© 2024 John Wiley & Sons Ltd.)

Background: Hepatocellular carcinoma (HCC) in autoimmune hepatitis (AIH) was considered rare but is increasing with prolonged prognosis. Its impact on the overall prognosis of AIH is unknown, and treatment has not been established., Aim: To investigate the risk factors and prognosis of HCC in patients with AIH and identify appropriate management strategies., Methods: We studied patients with AIH including background liver disease, sex, age, complications, treatment, response to treatment, liver fibrosis, prognosis, and treatment., Results: In 131 patients, deaths due to liver failure were more common early after the onset of AIH; however, deaths due to HCC increased gradually. HCC was observed in 12 patients (median age, 70 years; male/female, 4/8; cirrhosis at onset, 11; median time to carcinogenesis, 7 years). Cirrhosis at diagnosis was identified as a risk factor for carcinogenesis in the multivariate analysis (odds ratio, 41.36; p < 0.0001) and cumulative cancer rates were high. Multidisciplinary therapy other than immune checkpoint inhibitors was administered as treatment for HCC. Two of the three patients who used molecular-targeted drugs discontinued the treatment because of adverse events., Conclusion: HCC is an important cause of death in patients with AIH. Currently available drug therapies are limited and early detection is desirable., Trial Registration: This trial was retrospectively registered in the Ethics Committee of Kagawa University School of Medicine under the identifier 2019 - 238, registered on 4 Feb 2020., (© 2024. The Author(s).)

Purpose: To clarify the reproductive outcomes of fertility preservation (FP) treatment., Methods: We conducted a mailed-in questionnaire survey at institutions certified by the Japan Society of Obstetrics and Gynecology to investigate the number of oocyte cryopreservations (OC) and ovarian tissue cryopreservations (OTC) performed from December 2016 to the end of 2020. And, we conducted a detailed investigation of cases in which frozen specimens were used during the investigation period, and made historical comparisons with previous nationwide studies., Results: Responses were received from 114 out of 150 facilities (response rate: 76.0%) for OC and 43 out of 51 for OTC (response rate: 84.3%). Breast cancer was the most common disease among patients whose FP specimens were used. During the study period, 1237 OCs and 198 OTCs were performed. In addition, 57 cycles of embryo transfer (ET) using cryopreserved oocytes and 12 cases of ovarian tissue transplantation (OTT) were performed. The mean age of patients who underwent ET using cryopreserved oocytes was 34.8 (±5.8) years, with a median age of 36 years. The pregnancy rate per ET using cryopreserved oocytes was 26.3% and the live birth rate (LBR) was 17.5%. Further, the LBR per patient was 43.3%, and the pregnancy rate following OTTs was 33.3%. Also, controlled ovarian stimulation using the random start method or the combination of aromatase inhibitors had no effect on pregnancy outcome., Conclusion: Implementation of both OCs and OTCs have markedly increased over time in Japan, with comparable reproductive outcomes as other reports., (© 2024 Japan Society of Obstetrics and Gynecology.)

Invasive functional coronary angiography (FCA), an angiography-derived physiological index of the functional significance of coronary obstruction, is a novel physiological assessment tool for coronary obstruction that does not require the utilization of a pressure wire. This technology enables operators to rapidly evaluate the functional relevance of coronary stenoses during and even after angiography while reducing the burden of cost and complication risks related to the pressure wire. FCA can be used for treatment decision-making for revascularization, strategy planning for percutaneous coronary intervention, and procedure optimization. Currently, various software-computing FCAs are available worldwide, with unique features in their computation algorithms and functions. With the emerging application of this novel technology in various clinical scenarios, the Japanese Association of Cardiovascular Intervention and Therapeutics task force was created to outline expert consensus on the clinical use of FCA. This consensus document advocates optimal clinical applications of FCA according to currently available evidence while summarizing the concept, history, limitations, and future perspectives of FCA along with globally available software., (© 2024. The Author(s).)

Phytopathogenic bacteria (MAFF 302110 T and MAFF 302107) were isolated from lesions on Japanese angelica trees affected by bacterial soft rot in Yamanashi Prefecture, Japan. The strains were Gram-reaction-negative, facultatively anaerobic, motile with peritrichous flagella, rod-shaped, and non-spore-forming. The genomic DNA G+C content was 51.1 mol % and the predominant cellular fatty acids included summed feature 3 (C 16 : 1  ω7 c and/or C 16 : 1  ω6 c ), C 16 : 0 , summed feature 8 (C 18 : 1  ω7 c and/or C 18 : 1  ω6 c ), summed feature 2 (comprising any combination of C 12 : 0 aldehyde, an unknown fatty acid with an equivalent chain length of 10.928, C 16 : 1 iso I, and C 14 : 0 3OH), and C 12 : 0 . Phylogenetic analyses based on 16S rRNA and gyrB gene sequences, along with phylogenomic analysis utilizing whole-genome sequences, consistently placed these strains within the genus Pectobacterium . However, their phylogenetic positions did not align with any known species within the genus. Comparative studies involving average nucleotide identity and digital DNA-DNA hybridization with the closely related species indicated values below the thresholds employed for the prokaryotic species delineation (95-96 % and 70 %, respectively), with the highest values observed for Pectobacterium polonicum DPMP315 T (92.10 and 47.1 %, respectively). Phenotypic characteristics, cellular fatty acid composition, and a repertoire of secretion systems could differentiate the strains from their closest relatives. The phenotypic, chemotaxonomic, and genotypic data obtained in this study show that MAFF 302110 T /MAFF 302107 represent a novel species of the genus Pectobacterium , for which we propose the name Pectobacterium araliae sp. nov., designating MAFF 302110 T (=ICMP 25161 T ) as the type strain.

Background: Patients with Gaucher disease (GD), a rare lysosomal storage disorder, have reduced health-related quality of life (HRQOL). A patient-reported outcome measure (PROM) for HRQOL developed for type 1 GD (GD1) is not appropriate for patients with neuronopathic GD (nGD) types 2 (GD2) and 3 (GD3). In this study, we developed a new PROM for use in all GD types. We previously reported the qualitative analysis of interviews with Japanese patients with nGD, which was used to create nGD-specific PROM items. Here we evaluated the full PROM combining the type 1 questionnaire with the new nGD-specific items., Methods: Patients with confirmed GD were recruited (Association of Gaucher Disease Patients in Japan or leading doctors) for pre-testing (May 2021) or the main survey (October-December 2021). The PROM had three parts: Parts 1 and 2 were translated into Japanese from the pre-existing GD1 PROM, whereas Part 3 was newly developed. Patients (or their caregivers, where necessary) completed the PROM questionnaire on paper and returned it by mail. Mean scores were determined overall and by GD type. Inter-item correlations, content consistency (Cronbach's alpha), and test-retest reliability (Cohen's kappa; main survey only, taken 2 weeks apart) were calculated., Results: Sixteen patients (three with GD1; six with GD2; seven with GD3) and 33 patients (nine with GD1; 13 with GD2; 11 with GD3) participated in the pre-test and main survey, respectively. All GD2 patients and one-third (6/18) of GD3 patients required caregivers to complete the questionnaire. Mean scores indicated that the burden was highest in GD2 and lowest in GD1. In the main survey, internal consistency was high (Cronbach's alpha = 0.898 overall, 0.916 for Part 3), and test-retest reliability was high for Part 3 (kappa > 0.60 for 13/16 items) but low for Part 1 (kappa < 0.60 for 12/15 items)., Conclusions: We have developed a flexible and reliable PROM that can be tailored for use in all types of GD and propose using Parts 1 and 2 for GD1, Parts 2 and 3 for GD2, and Parts 1, 2, and 3 for GD3., (© 2024. The Author(s).)

Background: Among solid organ transplant (SOT) recipients, heart transplant (HT) recipients are at a higher risk of Toxoplasma gondii infection. As Toxoplasma seroprevalence varies by geographic location, updated local epidemiology is essential to guide preventive and therapeutic strategies. However, the Toxoplasma seroprevalence and incidence of post-transplant toxoplasmosis among SOT recipients in Japan are unknown., Methods: We performed a single-center retrospective observational study at an HT center in Tokyo, Japan. All HT recipients aged ≥18 years between 2006 and April 2019 were included. We reviewed patient charts and conducted a questionnaire survey to investigate the risk factors for infection., Results: Among 105 recipients included in the study, 11 (10.5%) were seropositive before transplant. Ninety-five recipients (90.5%), including all pre-transplant seropositive recipients, answered the questionnaire. The recipients who had lived in Okinawa (odds ratio [OR] 7.5 [95% CI 1.42-39.61]; P = .032) and who reported raw-meat eating habits (OR 4.64 [95% CI 1.04-23.3]; P = .021) were more likely to be seropositive. None of the patients developed symptoms of toxoplasmosis. The post-transplant incidence of other major adverse outcomes was not significantly different according to the pre-transplant serostatus., Conclusions: About 10% of HT recipients at an HT center in Tokyo were seropositive for Toxoplasma pre-transplant, and none developed symptomatic toxoplasmosis post-transplant on trimethoprim-sulfamethoxazole. The history of raw meat consumption was associated with seropositivity; therefore, avoiding it might be recommended for HT recipient candidates., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Heparin resistance is often encountered during cardiopulmonary bypass. Heparin dose and activated clotting time target values for the initiation of cardiopulmonary bypass are not yet universally standardized; further no consensus exists on the management of heparin resistance. This study aimed to investigate the current real-world practice on heparin management and anticoagulant treatment for heparin resistance in Japan., Methods: A questionnaire survey was conducted at medical institutions nationwide with which The Japanese Society of Extra-Corporeal Technology in Medicine members are affiliated, targeting surgical cases with cardiopulmonary bypass performed from January 2019 through December 2019., Results: Among 69% (230/332) of the participating institutions, the criterion for heparin resistance was defined as "the target activated clotting time value not reached even with an additional dose of heparin administration". Cases of heparin resistance were reported in 89.8% (202/225) of the responded institutions. Of note, 75% (106/141) of the responded institutions reported heparin resistance associated with antithrombin activity ≥ 80%. Antithrombin concentrate was used in 38.4% (238/619 responses) or third dose of heparin in 37.8% (234/619 responses) for advanced heparin resistance treatment. Antithrombin concentrate was found to be effective in resolving heparin resistance in patients having normal, as well as lower antithrombin activity., Conclusion: Heparin resistance has occurred in many cardiovascular centers, even among patients with normal antithrombin activities. Interestingly, the administration of antithrombin concentrate resolved heparin resistance, regardless of the baseline antithrombin activity value., (© 2023. The Author(s).)

Background: Low physical activity levels are associated with an increased risk of exacerbations and all-cause mortality in patients with chronic obstructive pulmonary disease (COPD); however, evidence is limited in a population with a low frequency of exacerbations, such as the Japanese population. This study investigated the effects of physical activity on outcomes in Japanese patients with COPD., Methods: We conducted a prospective observational study in a cohort of Japanese patients with COPD between April 2018 and July 2020. Characteristics, frequency of exacerbations, and mortality were assessed during the 1-year follow-up period. Logistic regression analysis evaluated the relationship between physical activity and outcomes., Results: A total of 309 patients (294 males; median age, 75 years) with stable COPD were included, and 307 completed follow-up. Patients with lower levels of physical activity were older, and showed increased airflow obstruction, limited exercise capacity, increased dyspnea, depressive state, poor health status, muscle weakness, and more information needs for the disease. Patients with high levels of physical activity had a lower risk of exacerbation, including hospital admission, compared to those with low levels of activity (odds ratio [OR], 0.46; 95 % confidence interval [CI], 0.22-0.97; and OR, 0.21; 95 % CI, 0.09-0.50, respectively). High physical activity was associated with a reduced risk of all-cause mortality (OR, 0.07; 95 % CI, 0.01-0.55) and respiratory mortality (OR, 0.16; 95 % CI, 0.02-1.47)., Conclusions: These findings showed that higher physical activity is associated with better clinical outcomes, even in a COPD population with a low frequency of exacerbations., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Our web-based training program called "Educating Medical Professionals about Reproductive Issues in Cancer Healthcare" aims to help healthcare professionals communicate promptly with patients and survivors who are adolescents and young adults, with information pertinent to reproductive health issues such as the risk of infertility and fertility preservation., Methods: The study participants were professional healthcare providers, including physicians, nurses, pharmacists, social workers, midwives, psychologists, laboratory technicians, genetic counselors, and dieticians. Pre- and post- and 3-month follow-up tests consisting of 41 questions were administered to measure changes in knowledge and confidence. The participants also received a follow-up survey that covered confidence, communication techniques, and practice habits. A total of 820 healthcare providers participated in this program., Results: The mean total score from the pre-test to the post-test grew significantly (p < 0.01), and participants' self-confidence increased. In addition, there was a change in the behavior of healthcare providers, who began asking about patients' marital status and parity., Conclusion: Our web-based fertility preservation training program improved knowledge and self-confidence regarding fertility preservation issues among healthcare providers caring for adolescents and young adult cancer patients and survivors., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Internationally, the prevalence of gambling disorder has been reported to be higher among homeless people than the general population; however, little is known about the factors associated with gambling disorder in this population. The present study aimed to investigate the prevalence of gambling disorder and its associated factors among homeless men using shelters in Osaka City. A cross-sectional survey was conducted from 30 to 2018 to 4 January 2019, using the 2017 Japanese National Survey of Gambling (JNSG) questionnaire, supplemented with questions about homeless experiences, drinking, and smoking. Using the South Oaks Gambling Screen, the presence of gambling disorder was determined by a score ≥ 5 out of 20. Multivariate logistic regression was conducted to explore factors associated with lifetime gambling disorder. Lifetime and past-year prevalence of gambling disorder among 103 participants was 43.7% (95% confidence interval [CI]: 34.5-53.3) and 3.9% (95% CI: 1.5-9.6), respectively, which are higher than the 6.7% and 1.5% found among men in the 2017 JNSG. Reasons reported for currently gambling less were primarily financial. Factors associated with lifetime GD included "more than 20 years since the first incidence of homelessness" (adjusted odds ratio [AOR]: 4.97, 95% CI: 1.50-16.45) and "more than five incidences of homelessness" (AOR: 4.51, 95% CI: 1.06-19.26). When homeless individuals with gambling disorder try to rebuild and stabilize their lives, the presence or resurgence of gambling disorder may hinder the process and pose a risk of recurring homelessness. Comprehensive support services for homeless individuals with gambling disorder are required. (250 words)., (© 2022. The Author(s).)

Purpose: Fertility preservation (FP) is becoming increasingly common among child, adolescent, and young-adult (CAYA) patients with cancer. However, Japan has long lacked definite estimates of utilization rates for FP services among CAYA patients with cancer, and little is known about disease/FP outcomes among users. Therefore, the Japan Society for Fertility Preservation (JSFP) launched the Japan Oncofertility Registry (JOFR) in 2018 and started the online registration of information regarding primary disease, FP, and data on prognosis and pregnancy outcomes. This study reports the analytical results of FP data registered in the JOFR as of 2021. Methods: Data about patients' primary disease(s), treatment courses, cancer and pregnancy outcomes, and specific procedures were extracted from the JOFR and analyzed. Results: In 2021, 1244 patients received counseling or treatment related to FP (540 males, 704 females). While the numbers of males in each age group were approximately equal, most females were aged between 31 and 40 years. In total, 490 male and 540 female patients underwent FP procedures. Leukemia, testicular cancer, and malignant lymphoma accounted for the majority of male cases seeking treatment, whereas breast cancer was the primary disease in two-thirds of the females. Since 1999, 395 patients have accumulatively experienced subsequent pregnancy. Conclusions: As of January 2022, >7000 cases from >100 fertility facilities have been registered in the JOFR. In the future, maintaining JOFR to disseminate information on cancer prognoses, pregnancy rates, and other oncofertility outcomes is expected to drive further expansion of oncofertility services in Japan.

The rapid naturalization of Bombus terrestris across the Nemuro Peninsula has led to a decline in two closely related native Japanese species, namely Bombus hypocrita sapporensis and Bombus cryptarum florilegus, both belonging to the common subgenus Bombus. Although it is widely believed that cross-mating of native and non-native species is influenced by the common male sex pheromone in this region, no study has been conducted to substantiate this claim. Thus, we investigated the cross-activities of male sex pheromones between native and non-native bumblebees, as well as the frequencies of cross-mating, using chemical and DNA assays. Our gas chromatography-electroantennographic detector analyses and behavioral tests revealed the presence of sex pheromonal cross-activities between B. terrestris and the two Japanese bumblebees species. Furthermore, DNA analyses revealed the occurrence of cross-mating between native and non-native species in the Nemuro Peninsula. Overall, these results indicate the immediate need for conservation measures to safeguard Japanese bumblebee populations in the Nemuro Peninsula., (© 2023. The Author(s).)

Background: Gaucher disease (GD) is a rare, inherited metabolic disorder resulting from glucocerebrosidase deficiency. Patients benefit from early treatment as complications can arise from delayed diagnosis., Aims: To measure GD awareness among Japanese haematologists and gastroenterologists, who are the specialists most likely to encounter patients with symptoms recognised in the Gaucher Earlier Diagnosis Consensus (GED-C), such as hepatosplenomegaly and thrombocytopenia. Additionally, we aimed to determine key signs from the GED-C associated with early diagnosis., Methods: A quantitative web survey assessed Japanese haematologists and gastroenterologists for their (i) basic awareness of GD, (ii) explicit awareness of GD signs, (iii) explicit awareness of GD treatments and (iv) accuracy in suspecting GD in model patients., Results: Survey results from 160 haematologists and 166 gastroenterologists indicated that more than 50% of haematologists were aware of GD symptoms, diagnostic criteria and/or treatments, and 38% of them had experienced or suspected GD. The majority of gastroenterologists were unaware of GD or knew the disease only by name, with 20% experiencing or suspecting GD in practice. Almost 70% of haematologists knew of enzyme replacement therapy, while 47% of gastroenterologists were not aware of any treatments for GD. Of the GED-C items, an awareness of bone-associated signs was correlated with accurate GD diagnosis in model patients and this awareness was greater among haematologists than gastroenterologists., Conclusions: The present study showed that haematologists had greater awareness of GD than gastroenterologists, and that bone pain may be a key sign of GD to enhance early diagnosis., (© 2022 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Background: Fulminant myocarditis (FM) is rare but has an extremely poor prognosis. Impella, a catheter-based heart pump, is a new therapeutic strategy, but reports regarding its health economics are lacking., Methods and results: This retrospective cohort study compared Impella treatment (Group I) with existing treatments (Group E) using medical data collected from October 2017 to September 2021, with a 1-year analysis period. Cost-effectiveness indices were life-years (LY; effect index) and medical fee amount (cost index). Results were validated using probabilistic sensitivity analysis. The incremental cost-effectiveness ratio (ICER) was calculated using quality-adjusted LY (QALY) and medical costs. Each group included 7 patients, and more than half (57.1%) received combined Impella plus extracorporeal membrane oxygenation. There was no significant difference between Groups I and E in 1-year mortality rates (28.6% vs. 57.1%, respectively) or LY (mean [±SD] 163.1±128.3 vs. 107.8±127.3 days, respectively), but mortality risk was significantly lower in Group I than Group E (95% confidence interval 0.02-0.96; P<0.05). Compared with Group E, Group I had higher total costs (9,270,597±4,121,875 vs. 6,397,466±3,801,364 JPY/year; P=0.20) and higher cost-effectiveness (32,443,987±14,742,966 vs. 92,637,756±98,225,604 JPY/LY; P=0.74), which was confirmed in the sensitivity analysis. ICER probability distribution showed 23.2% and 51.5% reductions below 5 million and 10 million JPY/QALY, respectively., Conclusions: Impella treatment is more cost-effective than conventional FM treatments. Large-scale studies are needed to validate the added effects and increasing costs.

Catheter-based micro-axial ventricular assist device Impella® (Abiomed, Danvers, MA) has been used in Japanese patients with drug-refractory acute heart failure (AHF) since 2017. This is the first interim analysis of the ongoing Japan Registry for Percutaneous Ventricular Assist Device (J-PVAD) to investigate the safety and efficacy of Impella support. Between October 2017 and January 2020, 823 Japanese patients, who were treated with the Impella 2.5, CP, or 5.0 pump, were enrolled. The primary endpoints were safety profiles and cumulative 30-day survival. Among them, 44.8% of patients were acute myocardial infarction with cardiogenic shock. The Impella pumps were unable to implant in 4 patients. The Impella 2.5, CP, and 5.0 pumps were used in 72.4%, 6.2%, and 16.6%, respectively, and mean support duration was 8.1 ± 10.2 days. Combination use of Impella and venoarterial extracorporeal membrane oxygenation (VA-ECMO) was applied for 387 patients (47.3%). Pump stop occurred 22 patients (2.7%). Major adverse events included hemolysis (11.2%), hemorrhage/hematoma (6.1%), peripheral ischemia (1.6%), and stroke (1.6%). The overall 30-day survival was 62.2%. Survival of patients with single Impella support was significantly higher than patients with Impella combined with VA-ECMO support (81.1% vs 49.6%; p < 0.01), who had lower blood pressure, lower left ventricular ejection fraction, and higher degree of inotropic support. Results suggest that short-term outcome of Impella support for Japanese patients was favorable with acceptable safety profiles., (© 2022. The Japanese Society for Artificial Organs.)

Purpose: This study investigated the association between menstrual symptoms and the intention to leave work among female nurses in Japan., Methods: This cross-sectional study investigated female nurses (n = 317) at two university hospitals. The items measured were their characteristics (e.g., age, body mass index), "intention to leave" work, somatic symptoms related with menstruation, self-reported menstrual characteristics (e.g., pain), physical workloads (e.g., working hours and night shifts) and psychological workloads, measured with the Copenhagen Burnout Inventory (CBI), and the Job Content Questionnaire (JCQ). Participants with at least four somatic symptoms (e.g., cold, fatigue) which are present during their menstrual cycles were considered to have "somatic symptoms associated with menstruation." We also measured serum ovarian and gonadotropin-releasing hormones., Results: Approximately 40% of women answered "intention to leave" work, and 17% had "somatic symptoms associated with menstruation." Multiple logistic regression analysis suggested that nurses reporting "somatic symptoms associated with menstruation" were more likely to have "intention to leave" work: the adjusted odds ratios (AOR, 95% confidence interval [CI]) were 2.15 (1.12-4.11) in the personal-burnout model, 2.23 (1.16-4.31) in the work-related burnout model, 2.91 (1.52-5.56) in the client-related burnout model; 2.96 (1.50-5.82) in the JCQ model. There was no association between serum and gonadotropin hormones and the intention to leave., Conclusion: Somatic symptoms with menstruation were associated with intention to leave work among female Japanese nurses. Intervention for somatic symptoms with menstruation might support nurses to continue work., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Digital therapeutics (DTx), the provision of treatment through mobile devices such as smartphones, have attracted great interest as a new medical modality. However, the number of authorized therapeutic applications in the US and Japan is low. Understanding the obstacles in obtaining regulatory authorizations will be the key in promoting timely development of therapeutic applications. Thus, we conducted a comprehensive analysis of the clinical study designs of therapeutic applications authorized in the US and Japan., Methods: Data on authorized therapeutic applications and the regulations involved were collated from the databases of the Food and Drug Administration (USA), Ministry of Health, Labour and Welfare (Japan), and Pharmaceuticals and Medical Devices Agency (Japan)., Results: Most therapeutic applications authorized targeted neuropsychiatric disorders and used cognitive behavioral therapy (CBT)-based treatments. All the involved clinical trials were randomized-controlled studies. Various types of controls-such as standard care, sham application, digital control, and therapies delivered by healthcare providers-were used. Both subjective and objective indices were acceptable as the primary endpoints. Long-term efficacy was evaluated, and all adverse events were assessed comprehensively. The setting up of controls and the need to study long-term efficacy depend heavily on the applications functionality and the target disease characteristics., Conclusions: This study reveals the points to be considered in planning clinical studies and regulatory strategies for authorizing therapeutic applications. Therapeutic applications can provide new therapy and have potential to solve unmet clinical needs. Our findings shed a light on efficient development and rapid commercialization of therapeutic applications., (© 2022. The Author(s).)

Aim: To investigate the status of abnormal uterine bleeding (AUB) in Japan using the International Federation of Gynecology and Obstetrics (FIGO) classification (AUB system 1 and 2; PALM-COEIN) and to clarify the relationship between AUB symptoms and the diseases causing AUB., Methods: In a nationwide study, we enrolled first-time patients who visited target facilities during two consecutive weeks from December 1, 2019 to January 31, 2020. The FIGO classification was used to investigate patients with symptoms and causative diseases of AUB. Based on the proportion of patients in the nationwide study, 373 cases were included in the detailed survey. Survey items included symptoms of AUB according to AUB system 1, examination details, and causative diseases according to the PALM-COEIN classification., Results: Within the study period, we encountered 61 740 first-time patients, of which 8081 (13.1%) were diagnosed with AUB. Among them, 39.9% had abnormal menstrual cycles and 56.9% had abnormal menstrual bleeding. In the survey, PALM had the highest percentage of AUB-L and COEIN had the highest percentage of AUB-O. Correspondence analysis showed that COEIN was strongly associated with abnormal menstrual cycles and PALM with abnormal menstrual bleeding., Conclusion: We conducted the first nationwide survey of AUB in Japan. The FIGO classification was a useful tool for the diagnosis of AUB, with a strong correlation between symptoms of AUB by AUB system 1 and the causative disease of AUB by PALM-COEIN. Conversely, a high percentage of AUB-N and AUB-E suggests that AUB system 1 and PALM-COEIN are ambiguous as diagnostic tools., (© 2022 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

In 2011, implantable ventricular assist device (iVAD) was initially approved in Japan as bridge-totransplant (BTT) indication. Since then, more than 1,300 iVAD implants were conducted as BTT, and this case number per year is rapidly increasing, especially after the approval of iVAD implant in 2021, as destination therapy (DT) indication. From now on, some of DT patients will be eventually registered for heart transplantation, once their exclusion criteria are cleared, thus extending waiting time of BTT patients, in the setting of serious donor shortage in Japan. Therefore, to improve the outcome of iVAD patients, both BTT and DT, it is imperative to manage device-associated complications, that can occur during prolonged long-term iVAD support. In the present review, we summarize the recent updates on the current trend and the future perspectives of iVAD treatment in Japan, in terms of the effect of DT approval on this treatment modalities and device-associated complications, specifically right ventricular failure and aortic regurgitation.

Background: The objective of this study is to investigate the effect of preoperative diabetes on all-cause mortality and major postoperative complications among patients with continuous-flow left ventricular assist device (LVAD) by using data from a national database., Methods and results: The 545 study patients who underwent primary HeartMateII implantation between 2013 and 2019 were divided into 2 groups according to their diabetes mellitus (DM) status; patients with DM (n=116) and patients without DM (n=429). First, the on-device survival and incidence of adverse events were evaluated. Second, after adjusting for patients' backgrounds, the change of laboratory data in the 2 groups were compared. Overall, on-device survival at 1, 2, and 3 years was almost equivalent between the 2 groups; it was 95%, 94%, and 91% in patients without DM, and 93%, 91%m and 91% in patients with DM (P=0.468) The incidence of adverse events was similar between 2 groups of patients, except for driveline exit site infection in the adjusted cohort. Cox proportional hazards regression analysis revealed younger age (HR: 0.98 (95% confidence interval (CI): 0.97-0.99, P=0.001) and presence of DM (HR: 1.83 (95% CI: 1.14-2.88), P=0.016) as significant predictors of driveline infection. Laboratory findings revealed no differences between groups throughout the periods., Conclusions: The clinical results after LVAD implantation in DM patients were comparable with those in non-DM patients, except for the driveline exit site infection.

The antigenic variant QX-like infectious bronchitis virus (IBV) is endemic in several countries. In Japan, the QX-like genotype is classified as the JP-III genotype based on the partial S1 gene and as the GI-19 genotype based on the complete S1 gene. This study showed that QX-like IBVs and JP-III IBVs can be identified based on the amino acid polymorphism of the S1 glycoprotein. Furthermore, genetic analysis of several IBV field strains detected in commercial broiler farms across the Kyushu area in 2020 revealed Japanese QX-like IBVs, which are highly homologous to the QX-like IBVs recently detected in China and South Korea. Herein, QX-like IBV field strains were isolated for evaluating commercial vaccine efficacy in our future studies.

Snow ecosystems are an important component of polar and mountainous regions, influencing water regime, biogeochemical cycles and supporting snow specific taxa. Although snow is considered to be one of the most unique, and at the same time a disappearing habitat, knowledge of its taxonomic diversity is still limited. It is true especially for micrometazoans appearing in snow algae blooming areas. In this study, we used morphological and molecular approaches to identify two tardigrade species found in green snow patches of Mt. Gassan in Japan. By morphology, light (PCM) and scanning electron microscopy (SEM), and morphometry we described Hypsibius nivalis sp. nov. which differs from other similar species by granular, polygonal sculpture on the dorsal cuticle and by the presence of cuticular bars next to the internal claws. Additionally, phylogenetic multilocus (COI, 18S rRNA, 28S rRNA) analysis of the second taxon, Hypsibius sp. identified by morphology as convergens-pallidus group, showed its affinity to the Hypsibiidae family and it is placed as a sister clade to all species in the Hypsibiinae subfamily. Our study shows that microinvertebrates associated with snow are poorly known and the assumption that snow might be inhabited by snow-requiring tardigrade taxa cannot be ruled out. Furthermore, our study contributes to the understanding subfamily Hypsibiinae showing that on its own the morphology of specimens belonging to convergens-pallidus group is insufficient in establishing a true systematic position of specimens., (© 2022. The Author(s).)

Background: Gaucher disease (GD) is a rare, autosomal recessive lysosomal storage disorder that adversely affects life expectancy and health-related quality of life (HRQOL). Although HRQOL questionnaires are available for type 1 GD, they are not suitable for patients with the neuronopathic types 2 and 3 GD who have neurological symptoms that develop during early childhood or adolescence. Here we report the development of a language-validated HRQOL questionnaire specifically for patients with neuronopathic types 2 and 3 GD in Japan, which is the first step toward HRQOL questionnaire provision for all types of GD in the future., Methods: In February and March 2021, semi-structured interviews were conducted by the authors (supported by qualified interviewers) with patients and/or their caregivers (for patients < 16 years old) who were recruited from a Japanese patient association, the Association of Gaucher Disease Patients in Japan. Qualitative analysis of interview transcripts was used to identify major themes and key topics within those themes. Hierarchical cluster analysis and co-occurrence network analysis were performed to map relationships between commonly occurring words. The study is registered at the UMIN Clinical Trials Registry ( https://www.umin.ac.jp/ctr/index.htm [UMIN000042872])., Results: Three main themes emerged from qualitative analysis: treatment status, patient burden, and social support systems. Key topics within each theme included hearing impairment, visual impairment, difficulty swallowing, difficulty speaking, involuntary movement of extremities, epileptic seizures, and body aches (treatment status); anxiety about symptoms, difficulty with exercise and work, anxiety about continuing treatment, anxiety about going out, and tiredness from hospital visit or treatment (patient burden); and dissatisfaction about government service, lack of social support, and information exchange in the patient association (social support systems). Commonly used words and the relationships between words identified through the hierarchical cluster and co-occurrence network analyses supported these themes and topics., Conclusions: The themes and topics identified in this analysis were specific to patients with types 2 and 3 GD and will be used to inform the development of a HRQOL questionnaire specifically for patients with all GD types., (© 2022. The Author(s).)

Background: Although many transplant programs have been forced to suspend living donor transplants due to the emergence of coronavirus disease (COVID-19), there are relatively few real-time databases to assess center-level transplant activities. We aimed to delineate the actual impact of COVID-19 on living donor transplant programs and the resumption process in Japan., Methods: In a nationwide survey, questionnaires were sent to 32 liver transplant programs that had performed at least more than one case of living donor liver transplantation in 2019 and 132 kidney transplant programs that had performed more than one living donor kidney transplantation in 2018., Results: Thirty-one (96.9%) and 125 (94.7%) liver and kidney transplant programs responded, respectively. In the early pandemic period, 67.7% (21/31) of liver programs and 29.8% (37/125) of kidney programs were able to maintain transplant activities similar to those during the pre-pandemic period. After temporal suspension, 58.1% of kidney programs resumed their transplant activity after the number of local COVID-19 cases peaked. Establishing institutional COVID-19 screening, triage, and therapeutic management protocols was mandatory to resume transplant activity for 64.5% and 67.7% of liver and kidney programs, respectively. In the future wave of COVID-19, 67.7% of liver programs would be affected by institutional COVID-19 intensive care unit-bound patient numbers, and 55.7% of kidney programs would stop if hospital-acquired severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection spreads., Conclusions: THIS NATIONWIDE SURVEY REVEALED FOR THE FIRST TIME HOW LIVING DONOR LIVER AND KIDNEY: transplant programs changed in response to the COVID-19 pandemic in a country where living donor transplantations are predominant., (© 2022 Wiley Periodicals LLC.)

Background: Under the revised heart allocation system in the United States, bridge to transplant (BTT) patients with left ventricular assist device (LVAD) have a longer waitlist period, as they are now lowly prioritized. However, little is known regarding the long-term trajectory of functional capacity (FC) and health-related quality of life (HR-QOL) among BTT-LVAD patients., Methods: We retrospectively analyzed 442 consecutive patients with BTT-LVAD between April 2013 and May 2019 from a Japanese nationwide registry. FC (New York Heart Association [NYHA] functional class, peak oxygen uptake [VO 2 ], and 6-min walk test [6MWT]) and HR-QOL (European Quality of Life [EQ-5D index] and Visual Analogue Scale [EQ-VAS]) were assessed at baseline and for up to 60 months after LVAD implantation., Results: During the follow-up period of 30 months (IQR 18-42 months), 100 (22.6%) patients underwent transplantation, 37 (8.3%) died, and 14 (3.1%) underwent explantation for recovery. Mean peak VO 2 , 6MWT distance, EQ-5D index, and EQ-VAS significantly improved 3 months after LVAD implantation (p = 0.0012, p = 0.0037, p < 0.001, p < 0.001, respectively). Furthermore, these improvements were sustained for up to 60 months following LVAD implantation. Major adverse events including device failure, infection, stroke, and bleeding, which occurred within the first 3 months after LVAD implantation may have not affected FC or HR-QOL for up to 60 months (p = 0.15, p = 0.22, respectively)., Conclusions: BTT patients showed long-term preservation of FC and HR-QOL, suggesting that BTT remains an option despite the long waiting time to HTx., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Long working hours are detrimental to physical and mental health. However, the association between long working hours and psychosomatic symptoms have remained controversial, possibly because of the existence of mediators between working hours and psychosomatic stress responses. We hypothesized that lifestyle habits, regarding sleep and mealtimes, act as mediators, and analyzed the associations between long working hours, sleep duration, mealtime regularity, and psychosomatic stress responses in office workers., Methods: From April 2017 to March 2018, an online cross-sectional survey regarding overtime work hours, work-related stress, sleep, and eating habits was conducted with employees of 17 companies located in Tokyo, Japan. Answers were obtained from 3559 employees, and 3100 provided written consent for the academic use of their answers, and were included in the analysis. A path analysis was conducted to assess the effect of overtime work on psychosomatic stress via shortened sleep or irregular mealtimes., Results: Overtime work hours had no direct effect on psychosomatic stress responses and depressive symptoms. However, overtime work hours affected sleep duration and the regularity of mealtimes. The effects of overtime work hours on psychosomatic stress responses and depressive symptoms were completely mediated by sleep duration and the regularity of mealtimes., Conclusion: Long working hours do not affect mental health directly; however, shortened sleep duration and irregular mealtimes mediate the effect of long working hours on psychosomatic stress responses and depressive symptoms.

Background: The Japan Environment and Children's Study (JECS) is a nationwide birth cohort study investigating environmental effects on children's health and development. A Sub-Cohort Study has begun, conducting extended exposure and outcome measurements by targeting a subgroup randomly selected from the JECS Main Study. We report the Sub-Cohort Study methodology and participants' baseline profiles., Methods: Of 100,148 children in the JECS Main Study, children born after April 1, 2013 who met eligibility criteria ([1] all questionnaire and medical record data from children and their mothers collected from the first trimester to 6 months of age, [2] biospecimens [except umbilical cord blood] from children and their mothers collected at first to second/third trimester and delivery) were randomly selected for each Regional Centre at regular intervals. Face-to-face assessment of neuropsychiatric development, body measurement, paediatrician's examination, blood/urine collection for clinical testing and chemical analysis, and home visits (ambient and indoor air measurement and dust collection) are conducted. Participants are followed up at 1.5 and 3 years old for home visits, and 2, 4, 6, and 8 years old for developmental/medical examination. The details of protocols after age 10 are under discussion., Results: Of 10,302 selected children, 5,017 participated. The profiles of the participating mothers, fathers and children did not substantially differ between the Main Study and Sub-Cohort Study., Conclusion: The JECS Sub-Cohort Study offers a platform for investigating associations between environmental exposure and outcomes.

Aims: Heart transplantation (HT) is an effective therapeutic option for end-stage heart failure. Infection is a major cause of morbidity and mortality after HT. Sarcopenia, defined as the loss of muscle mass and strength, is a common comorbidity in HT candidates with end-stage heart failure. However, the effects of sarcopenia on the occurrence of post-HT infections are not well understood. Therefore, we explored the association between the skeletal muscle mass and post-transplant infections in adult HT recipients., Methods and Results: We retrospectively examined the records of 135 patients who underwent HT between August 2007 and November 2019 at our institution. Pre-transplant computed tomography was used to calculate the skeletal muscle index (SMI) at the level of the third lumbar vertebra. Muscle wasting was defined as the SMI of the lowest sex-based tertiles. The primary endpoint was infections within 6 months of HT. The study included 109 patients (80 men, mean age: 41.6 ± 12.0 years): 37 patients in the muscle wasting group and 72 patients in the non-muscle wasting group. The mean SMI values in the muscle wasting and non-muscle wasting groups were 29.9 ± 4.8 cm 2 /m 2 and 40.7 ± 6.7 cm 2 /m 2 , respectively. Prior to HT, 108 (99.1%) patients were on left ventricular assist device support, and during that support, the rate of late right heart failure was significantly higher in the muscle wasting group than non-muscle wasting group (P = 0.012). Sixteen infections occurred within 6 months of HT. The most common infection sites included the respiratory tract (n = 5) and the upper gastrointestinal tract (n = 5), followed by the urinary tract (n = 4). Overall, 10 patients experienced infections in the muscle wasting group (27.0%) and 6 in the non-muscle wasting group (8.3%) (P = 0.009). Two patients in the muscle wasting group required intensive care unit admission, compared to none in the non-muscle wasting group. Low skeletal muscle mass was associated with infections in the univariate and multivariate logistic regression models (hazard ratio: 3.68, 95% confidence interval: 1.19-11.3; P = 0.023). However, the duration of all-cause mortality within 3 years did not differ between the groups (P = 0.56)., Conclusions: Low skeletal muscle mass is a predictor of post-HT infections within 6 months of HT., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The Japanese honeybee, Apis cerana japonica, shows a specific defensive behavior, known as a "hot defensive bee ball," used against the giant hornet, Vespa mandarinia. Hundreds of honeybee workers surround a hornet and make a "bee ball" during this behavior. They maintain the ball for around 30 min, and its core temperature can reach 46. Although various studies have been conducted on the characteristics of this behavior, its molecular mechanism has yet to be elucidated. Here, we performed a comprehensive transcriptomic analysis to detect candidate genes related to balling behavior., Results: The expression levels of differentially expressed genes (DEGs) in the brain, flight muscle, and fat body were evaluated during ball formation and incubation at 46 °C. The DEGs detected during ball formation, but not in response to heat, were considered important for ball formation. The expression of genes related to rhodopsin signaling were increased in all tissues during ball formation. DEGs detected in one or two tissues during ball formation were also identified., Conclusions: Given that rhodopsin is involved in temperature sensing in Drosophila, the rhodopsin-related DEGs in A. cerana japonica may be involved in temperature sensing specifically during ball formation., (© 2022. The Author(s).)

Aim: To assess the impact of breast-cancer treatment on fertility., Methods: We conducted a retrospective, case-based survey of treatments administered for infertility and pregnancy outcomes after patients underwent treatment for breast cancer. Surveys were distributed to breast oncology facilities and reproductive endocrinology and infertility (REI) facilities., Results: As high as 60% of the pregnancies in women under the age of 35 years occurred spontaneously. Additionally, the fertility rates decreased as age increased (under 35 years of age: 40%, 35-39 years of age: 21%, 40-44 years of age: 10%, respectively). In women who became pregnant after treatment for breast cancer, conception was achieved within 1 to 3 years after beginning to try for pregnancy., Conclusions: After treatment for breast cancer, women can expect spontaneous pregnancy, especially if they are under 35 years of age. It is important for patients 35 years of age and older to commence assisted reproductive technology in a timely manner when pursuing fertility after treatment for breast cancer., (© 2021 Japan Society of Obstetrics and Gynecology.)

In recent years, local governments in Japan have established a public financial support system for fertility preservation in pediatric, adolescent, and young adult cancer patients. Fertility preservation has become popular for patients with cancers included in the gonadal toxicity risk classification of the 2017 edition of the Guideline for Fertility Preservation in Children, Adolescents and Young Adult Cancer Patients from the Japan Society of Clinical Oncology. However, patients with cancer and non-cancer diseases that are not included in the Guideline's gonadal toxicity risk classification also often receive treatment that may affect fertility, but they are often denied the opportunity of fertility preservation because no public financial support is available for diseases not listed in the Guideline. The national research project proposes including these diseases in the indications and treatment for fertility preservation. Therefore, we cooperated with the Japan Society for Fertility Preservation and the Ministry of Health, Labour and Welfare research group to solicit opinions from experts in each therapeutic area and reviewed the literature and overseas guidelines. This paper summarizes the findings of the project. We believe that it will be an important source of information for clinicians treating patients who need fertility preservation but note that the appropriateness of fertility preservation for the disorders listed in this report needs to be continuously reviewed as medical care advances., (© 2021. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background and Purpose: The spread of COVID-19 has restricted the delivery of standard medical care to surgical patients dramatically. Surgical triage is performed by considering the type of disease, its severity, the urgency for surgery, and the condition of the patient, in addition to the scale of infectious outbreaks in the region. The purpose of this study was to evaluate the impact of the COVID-19 pandemic on the number of surgical procedures performed and whether the effects were more prominent during certain periods of widespread infection and in the affected regions., Methods: We selected 20 of the most common procedures from each surgical field and compared the weekly numbers of each operation performed in 2020 with the respective numbers in 2018 and 2019, as recorded in the National Clinical Database (NCD). The surgical status during the COVID-19 pandemic as well as the relationship between surgical volume and the degree of regional infection were analyzed extensively., Results: The rate of decline in surgery was at most 10-15%. Although the numbers of most oncological and cardiovascular procedures decreased in 2020, there was no significant change in the numbers of pancreaticoduodenectomy and aortic replacement procedures performed in the same period., Conclusion: The numbers of most surgical procedures decreased in 2020 as a result of the COVID-19 pandemic; however, the precise impact of surgical triage on decrease in detection of disease warrants further investigation., (© 2021. The Author(s).)

Objectives: Defining an adequate protein intake in older adults remains unresolved. We examined the association between calibrated protein intake and comprehensive frailty by sex in the Kyoto-Kameoka study., Design: Cross-sectional study of baseline data., Setting and Participants: The study included 5679 Japanese participants aged 65 years or older., Methods: Calibration coefficients were estimated from food frequency questionnaires and 7-day dietary records as a reference. Comprehensive frailty was evaluated using the 25-item Kihon Checklist (KCL) and defined as a total KCL score of ≥7points. Sex-specific calibrated protein intakes were presented as % of energy, per kg of actual body weight (BW), and per kg of ideal BW., Results: Multiple logistic regression analysis showed that calibrated protein intake is inversely associated with comprehensive frailty. The association between protein intake and comprehensive frailty was also evaluated using curve fitting with non-linear regression, a weak U-shaped association was found in males and an L-shaped association in females. Men had a low prevalence of frailty at a calibrated protein intake of 15-17% energy from protein, 1.2 g/kg actual BW/day, or 1.4 g/kg ideal BW/day, and women had a low prevalence of frailty at 17-21% energy from protein or 1.6 g/kg ideal BW/day, with the prevalence of frailty remaining unchanged at higher protein intakes. Meanwhile, the inverse relationship between protein intake per ABW and frailty showed a gradual decrease at 1.4 g/kg ABW/day for protein in women., Conclusions and Implications: A non-linear relationship was found between calibrated protein intake and frailty, with a U-shaped association in men and an L-shaped association in women. Adequate protein intake in healthy Japanese older adults was higher than the current recommended daily allowance., Competing Interests: This study was supported by Ajinomoto Co., Inc. Authors Yuki Okabe, Miho Ono, Tomonori Koizumi, and Hisamine Kobayashi are employed by Ajinomoto Co., Inc. This study is not related to any particular products of a company, and the results do not recommend any particular products. Yuki Okabe, Miho Ono, Tomonori Koizumi, and Hisamine Kobayashi contributed to the study design, interpretation of the data, and revision and approval of the manuscript.

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. While mitotane is the only agent approved for ACC, clinical data are scarce, especially in the Asian population. We reviewed 10 patients with ACC who received mitotane as a single agent or in combination with other agents in our institution. Patient characteristics, clinical outcomes, and toxicities were analyzed. Mitotane was administered to 2 patients as an adjuvant therapy and to 8 patients for systemic control. In the latter 8 patients, 1 patient had locally advanced disease and 1 had metastatic disease at the time of initial diagnosis, whereas the other 6 patients experienced metastatic relapse at mitotane initiation. The administered regimen was mitotane alone in 7 patients, and mitotane plus cytotoxic chemotherapy in 3 patients. The initial daily mitotane dose was 3.0 g in 2 patients, 1.5 g in 7 patients, and 1.0 g in 1 patient. The median duration of treatment was 3.7 (range, 0.7-22.1) months. In 8 systemic cases, the median overall survival from chemotherapy initiation was 7.2 months, and only 1 patient survived over 1 year. The median interval from mitotane termination to death in systemic cases was 2.8 months, and the cause was progressive disease in 4 patients and toxicity (hallucination, mycobacteriosis, or liver injury) in 3 patients. As a second-line regimen, 2 systemic cases and 1 adjuvant case were enrolled in clinical trials. Our analysis exhibited extremely poor prognosis under mitotane-based regimens, and further treatment strategies are warranted to improve outcomes.

Nonalcoholic fatty liver disease (NAFLD) has become a serious public health issue not only in Western countries but also in Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease that often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma (HCC). While a definite diagnosis of NASH requires liver biopsy to confirm the presence of hepatocyte ballooning, hepatic fibrosis is the most important prognostic factor in NAFLD. With so many NAFLD patients, it is essential to have an effective screening method for NAFLD with hepatic fibrosis. As HCC with non-viral liver disease has increased markedly in Japan, effective screening and surveillance of HCC are also urgently needed. The most common death etiology in NAFLD patients is cardiovascular disease (CVD) event. Gastroenterologists must, therefore, pay close attention to CVD when examining NAFLD patients. In the updated guidelines, we propose screening and follow-up methods for hepatic fibrosis, HCC, and CVD in NAFLD patients. Several drug trials are ongoing for NAFLD/NASH therapy, however, there is currently no specific drug therapy for NAFLD/NASH. In addition to vitamin E and thiazolidinedione derivatives, recent trials have focused on sodium glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) analogues, and effective therapies are expected to be developed. These practical guidelines for NAFLD/NASH were established by the Japanese Society of Gastroenterology in conjunction with the Japan Society of Hepatology. Clinical evidence reported internationally between 1983 and October 2018 was collected, and each clinical and background question was evaluated using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. This English summary provides the core essentials of these clinical practice guidelines, which include the definition and concept, screening systems for hepatic fibrosis, HCC and CVD, and current therapies for NAFLD/NASH in Japan., (© 2021. The Author(s).)

Increased variety and use of chemicals and the number of chemical disasters have changed chemical management. Europe and the United States have adopted self-regulation in chemical management; furthermore, countries worldwide must comply with the relevant United Nations recommendations and international standards for chemical management. Japan has experienced numerous pollution incidents and occupational disasters, resulting in the development of laws and regulations on chemical management; however, these policies are inconsistent with international trends. In particular, the shift from a compliance approach to self-regulation and measures for small businesses remain as challenges. This paper discusses the current situation and issues in chemical management in Japan, focusing on international trends.

Carbon monoxide diffusion capacity (DLCO) is impaired in heart failure patients; however, its clinical impact has not been well investigated in the left ventricular assist device (LVAD) population. We explored the predictive value of preoperative DLCO in the survival and cardiac readmission rates after LVAD implantation. Seventy-six patients who received continuous-flow LVAD as bridge-to-transplant therapy from November 2007 to September 2018 and underwent pulmonary function test before LVAD implantation were included. The primary study endpoints were death and readmission for heart failure or arrhythmia (cardiac readmission). Patients were stratified into two groups according to the percent of predicted DLCO (%DLCO). Pulmonary vascular resistance (PVR) was equivocal between the groups preoperatively, whereas the low DLCO group (%DLCO < 80%) showed significantly high PVR postoperatively. The mortality rate was not different between the groups. The 2 year cardiac readmission rate was 33.5% in the low DLCO group and 8.7% in the high DLCO group (%DLCO ≥ 80%) (P = 0.028). The %DLCO was associated with cardiac readmission in univariate and multivariate analyses (hazard ratio: 4.32; 95% CI: 1.50-15.9; P = 0.005). Low %DLCO was associated with high PVR postoperatively and was a risk factor for cardiac readmission after LVAD implantation., Competing Interests: Disclosure: E.A., M.H., and Y.H. belong to the Department of Therapeutic Strategy for Heart Failure, Graduate School of Medicine, University of Tokyo, which is endowed by Actelion Pharmaceuticals Japan Ltd., Otsuka Pharmaceutical, NIPRO CORPORATION, Terumo Corp., Senko Medical Instrument Mfg., Century Medical Inc., Kinetic Concepts Inc., St. Jude Medical. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

Destination therapy (DT) is the indication to implant a left ventricular assist device (LVAD) in a patient with stage D heart failure who is not a candidate for heart transplantation. The implantable LVAD has been utilized in Japan since 2011 under the indication of bridge to transplant (BTT). After almost 10 year lag, DT has finally been approved and reimbursed in May 2021 in Japan. To initiate the DT program in Japan, revision of the LVAD indication from BTT is necessary. Also, in-depth discussion of caregiver issues as well as end-of-life care is indispensable. For that purpose, we assembled a DT committee of multidisciplinary members in August 2020, and started monthly discussions via web-based communication during the COVID-19 pandemic. This is a summary of the consensus reached after 6 months' discussion, and we have included as many relevant topics as possible. Clinical application of DT has just started, and we are willing to revise this consensus to meet the forthcoming issues raised during real-world clinical experience.

Objective: The Emergency Severity Index (ESI) is a highly reliable and valid triage scale that is widely used in emergency departments in not only English language regions but also other countries. The Japan Triage and Acuity Scale (JTAS) is frequently used for emergency patients, and the ESI has not been evaluated against the JTAS in Japan. This study aimed to examine the decision accuracy of the ESI for simulated clinical scenarios among nursing specialists in Japan compared with the JTAS., Method: A parallel group randomized trial was conducted. In total, 23 JTAS-trained triage nurses from 10 Japanese emergency departments were randomly assigned to the ESI or the JTAS group. Nurses independently assigned triage categories to 80 emergency cases for the assessment of interrater agreement., Results: Interrater agreement between the expert and triage nurses was κ = 0.82 (excellent) in the ESI group and κ = 0.74 (substantial) in the JTAS group. In addition, interrater agreement by acuity was level 2 = 0.42 (moderate) in the ESI group and level 2 = 0.31 (fair) in the JTAS group. Interrater agreement for triage decisions was classified in a higher category in the ESI group than in the JTAS Scale group at level 2. Triage decisions based on the ESI in Japan maintained the same level of interrater agreement and sensitivity as those in other countries., Conclusion: These findings suggest that the ESI can be introduced in Japan, despite its different emergency medical background compared with other countries., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cleanliness of milking equipment is known to be important for the safety of dairy products and to prevent the spread of diseases among cows. We investigated the cleaning procedures of milking equipment and suckling equipment on Japanese dairy farms, and the cleanliness of bucket milkers, suckling buckets, milk receivers, and bulk tanks, using adenosine triphosphate (ATP) bioluminescence test. Bulk tanks (except one bulk tank) and milk receivers were washed by automated cleaning, but all bucket milkers and suckling buckets were washed by manual cleaning. Detergents were often not used to clean bucket milkers and suckling buckets. The log 10 transformed relative luminescence units (LRLU) of equipment washed by manual cleaning was higher than equipment washed by automated cleaning. Clean surfaces (≤2.2 LRLU) were only observed on the bulk tank and the milk receiver. More than 50% of the LRLU of the mouthpiece, the rubber packing of claw, and the nipple of the suckling bucket were determined dirty. These results suggest that the cleanliness of the bucket milkers and the suckling buckets washed by manual cleaning was lower than that of the equipment washed by automated cleaning, and may be due to insufficient cleaning procedures.