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The final disposal of the soils removed from the area affected by the Fukushima nuclear accident will be carried out by 2045. This study investigated how acceptance of final disposal differed between top-down, opinion-aggregative, and opinion-reflective approaches to the decision outcome, and what factors influenced these differences. In 2022, a survey of 3000 randomly selected participants living outside Fukushima Prefecture was conducted using the postal method, with responses obtained from 871 consenting participants. The proportions of respondents who agreed to accept the final disposal were 22.6, 37.6 and 56.9% for the top-down, opinion-aggregative, and opinion-reflective approaches, respectively. The preferences for both opinion-aggregative and opinion-reflective approaches showed significant positive associations with interest in final disposal and social benefits, and significant negative associations with intergenerational expectations and age. This study highlights the importance of procedural fairness in determining final disposal sites, and identifies factors that contribute to greater acceptance through this process., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Mini-endoscopic combined intrarenal surgery (ECIRS) offers improved advantages in the treatment of renal stones. However, the factors influencing the operative time remain poorly understood. This study aimed to identify the factors that enhance treatment planning and minimize complications. Clinical data from consecutive patients who underwent mini-ECIRS for renal stones and achieved a stone-free status between 2015 and 2021 at three high-volume centers in Japan were analyzed. The final treatment outcome was evaluated by computed tomography imaging at postoperative 1 month, and a successful outcome was defined as complete stone-free or residual stone fragments < 4 mm. Logistic and linear regression models were used to predict the operative duration of mini-ECIRS. An operative time of ≥ 120 min was significantly associated with punctured pole and body mass index (BMI), and septic shock was only observed in patients with operative times of ≥ 120 min. The multivariate model for the operative time for mini-ECIRS identified five clinical factors: punctured pole, number of stones, number of involved calyces, BMI, and preoperative nephrostomy. We believe these findings will help surgeons and patients plan suitable treatment strategies, predict the additional need for a second mini-ECIRS or retrograde intrarenal surgery alone, and avoid severe complications., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: While respiratory syncytial virus (RSV) is one of the most common pathogens in adults admitted to the ICU due to respiratory diseases, no reports regarding the occurrence rate of RSV infections in adults in Japan during the COVID-19 pandemic exist., Patients and Methods: We conducted this retrospective study to examine the exact occurrence rate of RSV infections in adults. We reviewed all patients (≥18 years) with any respiratory symptoms who received quantitative polymerase chain reaction (PCR) using nasopharyngeal samples for respiratory viruses by GeneLEAD at the Aichi Medical University Hospital between November 2022 and November 2023., Results: A total of 541 adult patients who underwent PCR test were enrolled in this study. RSV was identified in 18 cases (3.3 %); 8 (1.5 %) upper and 10 (1.8 %) lower respiratory tract infections. Influenza A and SARS-CoV-2 were found in 10 (1.8 %) and 61 (11.3 %), respectively. Patients with RSV infections and COVID-19 had more comorbidities than those with Influenza virus infections. As for RSV-associated with lower respiratory tract infection cases, 10 developed acute respiratory failure, resulting in 1 fatal case due to pneumonia and 1 died of septic shock due to ileus. The 30-, 90-day mortality rates were 1 (6 %) and 2 (11 %) respectively., Conclusion: About 3 % of adults had RSV infections during the COVID-19 pandemic. The outcomes of RSV infections in adults were similar to those by COVID-19. Those with comorbidities should have a preventive method against RSV infections, the same as for COVID-19., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Primary Percutaneous Coronary Intervention (PCI) has significantly contributed to reducing the mortality of patients with ST-segment elevation myocardial infarction (STEMI) even in cardiogenic shock and is now the standard of care in most of Japanese institutions. The Task Force on Primary PCI of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) proposed an expert consensus document for the management of acute myocardial infarction (AMI) focusing on procedural aspects of primary PCI in 2018 and updated in 2022. Recently, the European Society of Cardiology (ESC) published the guidelines for the management of acute coronary syndrome in 2023. Major new updates in the 2023 ESC guideline include: (1) intravascular imaging should be considered to guide PCI (Class IIa); (2) timing of complete revascularization; (3) antiplatelet therapy in patient with high-bleeding risk. Reflecting rapid advances in the field, the Task Force on Primary PCI of the CVIT group has now proposed an updated expert consensus document for the management of ACS focusing on procedural aspects of primary PCI in 2024 version., (© 2024. The Author(s).)

Purpose: The prevalence of airflow obstruction in Japan is 3.8%-16.9%. This epidemiological study based on a large database aimed to reassess the prevalence of airflow obstruction in Japan and the diagnosis rate of chronic obstructive pulmonary disease (COPD)., Patients and Methods: We used data regarding claims from the health insurance union and health checkups provided by JMDC. The present study included a subgroup of individuals aged ≥40 years who underwent health checkups involving spirometry between January and December 2019. The study endpoints were the prevalence of airflow obstruction, COPD diagnosis rate, disease stage, and respiratory function test results., Results: Among 102,190 participants, 4113 (4.0%) had airflow obstruction. The prevalence of airflow obstruction was 5.3% in men and 2.1% in women. Among the study population, 6.8% were current smokers, while 3.4% were never or former smokers. Additionally, the prevalence of COPD increased with age. Approximately 8.4% of participants with airflow obstruction were diagnosed with COPD. Regarding the COPD diagnosis status, participants with airflow obstruction who were diagnosed with COPD were at a more advanced stage than those not diagnosed. Finally, patients diagnosed with COPD had significantly lower FEV 1 /FVC and FEV 1 (p < 0.0001; Wilcoxon rank sum test)., Conclusion: The epidemiological study based on a large database determined the COPD diagnosis rate related to airflow obstruction. The COPD diagnosis rate was extremely low among individuals who underwent health checkups, indicating the need for increased awareness about this medical condition. Moreover, primary care physicians should identify patients with suspected COPD and collaborate with pulmonologists to facilitate the early detection of COPD and enhance the COPD diagnosis rate., Competing Interests: YK, SD, TM, and AS are employees of Kracie, Ltd. GT and TT are affiliated with JMDC Inc. YS and HS received personal fees from Kracie, Ltd. The authors report no other conflicts of interest in this work., (© 2024 Koga et al.)

Radioactively contaminated soil from the Fukushima Daiichi nuclear power station accident in 2011 is required by law to be finally disposed of outside Fukushima Prefecture by 2045. To gain public acceptance of this policy, it is essential to promote understanding and nationwide discussion. We conducted a web-based survey of 2000 people in Japan to examine public attitudes toward final disposal of the contaminated soil outside Fukushima Prefecture. Results show that policy approval was negatively correlated with perceived risk of a final disposal site, sense of inequity associated with building a final disposal site near residential areas, and values that are absolutely non-negotiable or protected from trade-offs with other values (protected values). Policy approval was positively correlated with high levels of interest in the Fukushima accident and subjective knowledge of decontamination and the policy. Respondents' comments and opinions about the policy indicated that respondents who approved of the policy accepted burden sharing, while those who disapproved were unconvinced by the rationale behind disposal outside Fukushima Prefecture and were dissatisfied by the lack of information disclosure and transparency. While the government's efforts to disseminate information about the current status and future of Fukushima have been effective to a certain extent, they are insufficient to achieve widespread public understanding of the policy. Our results indicate that attention needs to be paid to procedural fairness and explanations of risks., (© 2024. The Author(s).)

Objective Pulmonary function tests are essential for diagnosing respiratory diseases, such as chronic obstructive pulmonary disease (COPD), but are typically not performed in Japan during annual health checkups, which hinders the early diagnosis of respiratory diseases. Methods Individuals who agreed to participate in the Yamagata-Takahata study during medical checkups in Takahata (Yamagata Prefecture, Japan) in 2011 were examined. We interviewed 669 participants (49.0% men; mean age, 67.7 years old) regarding their respiratory symptoms and smoking habits and performed pulmonary function tests during the study. Results Based on pulmonary function test results, 141 participants had pulmonary dysfunction, and 115 had obstructive pulmonary dysfunction. The risk of respiratory dysfunction, particularly obstructive respiratory dysfunction, was examined by referring to a questionnaire tool for an early COPD diagnosis. The associations between age, the smoking history, respiratory symptoms, and obstructive respiratory dysfunction were evaluated. Obstructive respiratory dysfunction was found in 17.6% of participants ≥50 years old and 19.5% ≥60 years old, 30.3% had a smoking history, and 32.8% had respiratory symptoms. Furthermore, the participants with multiple factors had a higher probability of obstructive respiratory dysfunction. Conclusion Subjects with obstructive pulmonary dysfunction are expected to be efficiently identified by extracting individuals by age and smoking habit and through a respiratory symptom questionnaire, although pulmonary function tests cannot be performed for all individuals during health checkups.

Purpose: Anaerobic bacteria, existing on human skin and mucous membranes, can cause severe infections with complications or mortality. We examined the clinical characteristics of patients infected with Fusobacterium spp. and assessed their antibiotic susceptibility., Methods: Clinical data were collated from patients diagnosed with Fusobacterium infections in a Japanese university hospital between 2014 and 2023. Antibiotic susceptibility tests were conducted following the Clinical and Laboratory Standards Institute guidelines., Results: We identified 299 Fusobacterium isolates. The median age was 61 years (range, 14-95 years), with females constituting 43.1% of the patients. Most infections were community-acquired (84.6%, 253/299). Multiple bacterial strains were isolated simultaneously in 74.6% of cases. One-fourth of the patients had solid organ malignancies (25.4%, 76/299), and 14.5% (11/76) of those had colorectal cancer. The 30-day mortality rate was 1.3%. Fusobacterium species were isolated from blood cultures in 6% (18/299) of the patients. Patients, aged 75 years or older, with cerebrovascular disease or hematologic malignancy exhibited significantly higher prevalence of blood culture isolates in univariate analysis. Each Fusobacterium species had its characteristic infection site. Approximately 5% F. nucleatum and F. necrophorum isolates showed penicillin G resistance. Moxifloxacin resistance was observed in varying degrees across strains, ranging from 4.6 to 100% of isolates. All isolates were sensitive to β-lactam/β-lactamase inhibitors, carbapenems, and metronidazole., Conclusion: We show a link between Fusobacterium species and solid organ malignancies. We observed resistance to penicillin, cefmetazole, clindamycin, and moxifloxacin, warranting caution in their clinical use. This study offers valuable insights for managing Fusobacterium infections and guiding empirical treatments., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

For adult anuran amphibians, the kidney and urinary bladder play important osmoregulatory roles through water reabsorption. In the present study, we have examined ontogenetic expression of aquaporins, i.e., AQP2, AQPamU (AQP6ub, AQPa2U), and AQP3, in these organs using the Japanese tree frog, Dryophytes japonicus . Immunohistochemistry using the metamorphosing larvae at stages 40-43 localized AQP2 protein to the collecting ducts in the dorsal zone of the mesonephric kidney. At prometamorphic stages 40 and 41, labelling of AQP2 protein was observed in the apical/ subapical regions of the collecting duct cells. At climax stages 42 and 43, labels for AQP2 and AQP3 became observed in the apical/subapical regions and basolateral membrane of the collecting duct cells, respectively, as seen in the adults. As for the urinary bladder, immuno-positive labels for AQPamU were localized to the apical/subapical regions of granular cells in the mucosal epithelium at stages 40-43. On the other hand, AQP3 immunoreactivity was hardly observed in the urinary bladder at stage 40, and weakly appeared in many granular cells at stage 41. Thereafter, labels for AQP3 became evident along the basolateral membrane of granular cells at stages 42 and 43, together with AQPamU in the apical/subapical regions. These results suggest that the kidney and urinary bladder might be capable of water reabsorption, via AQP2, AQPamU, and AQP3, at stage 42, contributing to the acclimation of the tree frogs to terrestrial environments.

Objectives: Occupational future time perspective (OFTP) is important concept for a successful career in older workers. The purpose of this study was to examine the associations between individual and work-related factors and OFTP., Methods: We conducted a cross-sectional study via an online questionnaire survey. Respondents were stratified sampled according to the distribution of workers across Japan. To assess OFTP, we used the Japanese version of the OFTP scale. We included factors such as sex, age, education, marital status, subjective health status, personal income, length of employment, industry, size of company, employment status, working days per week, and night shift. Multiple regression analysis was employed to calculate the regression coefficients for each factor, with OFTP serving as the dependent variable., Results: In total we included 1484 respondents. Our findings indicated that higher OFTP was associated with higher education, better subjective health status, higher personal income, and smaller size of company. Compared with manufacturing, certain industries such as agriculture and forestry, transportation and postal services, and health care showed lower OFTP. In contrast to permanent workers, contract and part-time workers demonstrated lower OFTP, whereas owners of non-family businesses exhibited higher OFTP. Furthermore, individuals working 1-4 d/wk showed lower OFTP compared with those working 5 d/wk., Conclusions: Older workers facing limitations in resources, such as educational background, personal income, precarious employment, and health status, tend to have lower OFTP. Such individuals should be given priority for support and assistance., (© The Author(s) [2024]. Published by Oxford University Press on behalf of Journal of Occupational Health.)

In Japan, approximately 30% of spinocerebellar degeneration (SCD) is hereditary, and more than 90% of hereditary SCD is autosomal dominant SCD (AD-SCD). We have previously reported the types of AD-SCD in Hokkaido, twice. In this study, we investigated the status of AD-SCD mainly due to repeat expansions, covering the period since the last report. We performed genetic analysis for 312 patients with a clinical diagnosis of SCD, except for multiple system atrophy at medical institutions in Hokkaido between January 2007 and December 2020. The median age at the time of analysis was 58 (1-86) years. Pathogenic variants causing AD-SCD due to repeat expansion were found in 61.5% (192 cases). Spinocerebellar ataxia (SCA) 6 was the most common type in 25.3% (79 cases), followed by Machado-Joseph disease (MJD)/SCA3 in 13.8% (43), SCA1 in 6.4% (20), SCA2 in 5.1% (16), SCA31 in 4.8% (15), dentatorubral-pallidoluysian atrophy in 4.8% (15), SCA7 in 0.6% (2), and SCA8 in 0.6% (2). SCA17, 27B, 36, and 37 were not found. Compared to previous reports, this study found a higher prevalence of SCA6 and a lower prevalence of MJD/SCA3. An increasing number of cases identified by genetic testing, including cases with no apparent family history, accurately revealed the distribution of disease types in Hokkaido., (© 2023. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

The coronavirus disease (COVID-19) pandemic continues to threaten global public health. Remdesivir and monoclonal antibodies have shown promise for COVID-19 treatment of patients who are immunocompromised, including those with cancer, transplant recipients, and those with autoimmune disorder. However, the effectiveness and safety of this combination therapy for patients who are immunosuppressed remain unclear. We compared the efficacy and safety of combination therapy and remdesivir monotherapy for patients with mild-to-moderate COVID-19 who were immunosuppressed. Eighty-six patients treated in July 2021-March 2023 were analyzed. The combination therapy group (CTG) showed a statistically significant reduction in viral load compared with the monotherapy group (MTG) ( p < 0.01). Patients in the CTG also experienced earlier resolution of fever than those in the MTG ( p = 0.02), although this difference was not significant in the multivariate analysis ( p = 0.21). Additionally, the CTG had significantly higher discharge rates on days 7, 14, and 28 than the MTG ( p < 0.01, p < 0.01, and p = 0.04, respectively). No serious adverse events were observed with combination therapy. These findings suggest that combination therapy may improve the clinical outcomes of immunosuppressed COVID-19 patients by reducing the viral load and hastening recovery. Further studies are required to fully understand the benefits of this combination therapy for immunocompromised COVID-19 patients.

Background: Preconception care is not widespread in Japan and there is a pressing need to improve the practice. The present study assessed the knowledge and behavior of preconception care among women to seek effective intervention. Our research questions were: 1) How much do women know about preconception care? 2) How much are they practicing preconception care and what are the information sources of their behavior? 3) Do the women's preconception care behavior associated with accurate knowledge?, Methods: The research was conducted in a rural town in central Japan. Using an exploratory sequential mixed methods design, we undertook interviews, developed a survey based on the qualitative results, and then conducted a survey. The interviews explored how preconception care was perceived and practiced in women of childbearing age. The survey was designed to investigate the knowledge of preconception care among women with and without pregnancy experience, their practice behavior of preconception care, and whether the behavior is associated with knowledge., Results: The participants were 13 for the interview and 232 for the survey. They had limited access to preconception care recommendations and advice for specific actions was given by obstetricians and gynecologists after pregnancy. There was a large gap in knowledge about preconception care between parous and nulliparous women, especially about the need for folic acid supplementation. Practices that were manageable in their daily lives, such as cessation of smoking and alcohol, diet, and weight management, were considered common sense. In contrast, recommended practices that require medical attention, such as screening for sexually transmitted diseases and cervical cancer, tended to be less accurately known and practiced. Participants' sources of information about preconception care were the Internet, family and friends and mass media., Conclusion: In rural Japan, women of childbearing age lack knowledge about preconception care, especially before their first pregnancy. Primary care providers should try outreach to schools and women's groups in the community, promote information sharing among family and close friends, and utilize information technology to enhance the knowledge and practice of preconception care., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective Hereditary ATTR (ATTRv) amyloidosis was once an incurable disease; however, in recent years, disease-modifying therapies, such as tafamidis and patisiran, have become available. We herein report the medical care situation in an ATTRv amyloidosis non-endemic area of Japan. Methods We confirmed the information in the medical records of our department and analyzed the data retrospectively. Patients Patients with ATTRv amyloidosis who were treated in our department between 2010 and 2021 were included. Results A total of 15 ATTRv amyloidosis cases (8 men and 7 women) were treated in our department during the study period; 9 patients had a family history, and the transthyretin V30M (p.V50M) gene mutation was present in 66% of cases. The average age of the onset was 57 years old, with 73% of the initial symptoms being dysesthesia and 13% being autonomic dysfunction. Ten patients were treated with tafamidis and nine with patisiran. Although it took a long time to start treatment among our experienced cases, there were some cases in which treatment could be introduced relatively early. Conclusion ATTRv amyloidosis is treatable and should be included in the differential diagnosis of neuropathy so that it can be diagnosed early and introduced into treatment. In the near future, the presymptomatic diagnosis of ATTRv amyloidosis and genetic counseling will become more important.

Psoriasis patients have been reported to have a higher prevalence of nonalcoholic fatty liver disease (NAFLD), therefore detection at an early stage is important since it may progress to hepatic cirrhosis or hepatocellular carcinoma. We evaluated liver fat accumulation in patients with moderate to severe psoriasis by chest computed tomography (CT). The images were taken for screening purposes prior to the start of any biologics. The prevalence of NAFLD in patients with psoriasis vulgaris, psoriatic arthritis, and control subjects was 19.4%, 33.3% and 9.8%, respectively (P = 0.004). The mean CT score in psoriasis patients was significantly lower (51.684 ± 12.778) than that in control subjects (61.204 ± 9.498, P < 0.001). Multivariate logistic regression analysis showed that only CT scores were associated with the presence of psoriasis (P = 0.001). No significant relationship was observed between the Psoriasis Activity and Severity Index scores and CT scores of psoriasis patients (P = 0.055), suggesting that the presence of psoriasis may contribute to the pathogenesis of NAFLD. By analysis of chest CT imaging, our study successfully assessed liver fat accumulation. Chest CT is a useful diagnostic tool for the quantitative measurement of fat accumulated in the liver, enabling the early noninvasive detection of NAFLD and early therapeutic intervention., (© 2022 Japanese Dermatological Association.)

Background: Successful implantation of the WATCHMAN device requires an accurate understanding of left atrial appendage (LAA) anatomy and orifice dimensions. Racial differences are observed in LAA size when comparing Asians with non-Asians., Methods: A total of 170 patients (123 male, 67.4 ± 9.2 years) with paroxysmal or persistent atrial fibrillation (AF) underwent transesophageal echocardiography before catheter ablation or cardioversion (September 2018 to September 2019). As per the recommendations of the WATCHMAN device, the maximal LAA ostial diameters were measured at multiplane angles of 0°, 45°, 90°, and 135°., Results: The majority of patients (121/170, 71%) had an LAA orifice size within 17-25 mm. Fifteen (8.8%) patients had undersized (< 17 mm) and eight (0.5%) had oversized (> 31 mm) LAA. One patient in this population had no LAA. LAA size was significantly larger in patients with persistent AF than in those with paroxysmal AF (23.3 ± 4.2 mm vs. 20.0 ± 3.0 mm, p < 0.001) and in male patients than in female patients (22.4 ± 4.2 vs. 20.9 ± 3.7 mm, p = 0.03). LAA orifice dimension was significantly correlated with CHADS 2 score, the left atrial volume (LAV), E/e', and the left ventricular ejection fraction. Persistent AF, body mass index, and LAV were independently associated with LAA orifice dimension in multivariate analysis., Conclusion: This study demonstrated the distribution of LAA orifice dimension in the Japanese AF patients. This finding should be used as a reference to understand the racial characteristics of LAA size for the WATCHMAN procedure., (© 2022. Japanese Society of Echocardiography.)

As therapies for hereditary neuromuscular diseases are developed, the need for presymptomatic genetic testing and genetic counseling for early treatment is expected to increase. In Japan, there is no uniformly recommended protocol for presymptomatic genetic testing. In order to provide basic data for the establishment of a presymptomatic genetic testing system, we surveyed medical genetics departments in Japan about their current status (response rate: 67.4%). The questionnaire survey revealed that approximately 60% of facilities had established their own procedures for presymptomatic genetic testing, but the approaches used varied from facility to facility. The interview survey enabled us to identify the essential factors for the establishment of a presymptomatic genetic testing system for each case, each facility, and at the overall level. In the future, there is a need to develop a standardized protocol to help establish a presymptomatic genetic testing system.

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge 1-5 . Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target., (© 2022. The Author(s).)

Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection., (© 2022. The Author(s).)

This brief report documents the results of a survey that measured the public's and doctors' perceived effectiveness of preventive behaviors against COVID-19, in Japan. Medical doctors ( n  = 117) and the general public ( n  = 1086) participated in our online survey. The results of the analysis of mean scores indicate that there were only slight differences in perceived effectiveness between the two groups, while the differences in distributions were remarkable. The results of Silverman's test suggest the unimodality of doctors' responses and multimodality of the public's responses. Implications of the findings to combat the risk of infection are discussed.

Background: This study aimed to examine whether modifiable risk factors can predict tooth loss over 10 years and estimate population attributable risk (PAR) for a combination of modifiable factors., Methods: This longitudinal study included 1466 participants who underwent dental examinations in 2007 and 2017 and were aged 40 to 79 years at baseline. Periodontal conditions were assessed using the 2018 periodontal classification. Incident tooth loss was defined as ≥4 teeth lost over a 10-year period. We calculated the partial PAR (pPAR%) for tooth loss to estimate the combined effect of modifiable risk factors., Results: Incidence of tooth loss was 17.5%. Directed acyclic graphs were used to identify risk factors for tooth loss. A logistic regression model showed that baseline periodontitis, dental caries experience, no regular dental visit, periodontal treatment, smoking, and obesity were associated with tooth loss after adjusting for covariates; pPAR% was 55.5% (95% confidence interval: 31.1% to 73.0%) in periodontitis Stage III to IV and 87.6% (50.4% to 97.4%) in the combination of all factors, respectively. The sex-stratified analysis showed that smoking and no regular dental visit in men and obesity in women were identified as potential risk factors for tooth loss., Conclusions: Modifiable factors accounted for most cases of incident tooth loss. Risk factors for tooth loss might differ by sex, suggesting that the appropriate approach for preventing tooth loss base on sex., (© 2021 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)

Purpose: The purpose of the J-SUPREME (J-S) and J-SUPREME II (J-SII) trials was to evaluate the performance of the Jetstream Atherectomy System for the treatment of Japanese patients with symptomatic occlusive atherosclerotic lesions in the superficial femoral and popliteal arteries., Materials and Methods: The J-S and J-SII trials were both prospective, multicenter, single-arm clinical trials. Patients in J-S underwent Jetstream atherectomy followed by percutaneous transluminal angioplasty (PTA), whereas those in J-SII had adjunctive drug-coated balloon (DCB) treatment following atherectomy. Patients were adults with Rutherford category 2, 3, or 4 and had stenotic, restenotic, or occlusive lesion(s) with a degree of stenosis ≥70 in the superficial femoral artery and/or proximal popliteal artery. In J-S, lesions were required to be calcified, and in J-SII lesions were required to be severely calcified., Results: A total of 50 patients were enrolled in J-S (mean age 72.3±8.7 years, lesion length 82.0±41.5 mm, 36% calcification PACSS Grade 3, 22% Grade 4) and 31 patients in J-SII (mean age 72.5±7.7 years, lesion length 122.6±55.6 mm, 19.4% calcification PACSS Grade 3, 77.4% Grade 4). No bailout stenting or bypass conversions were required. No major adverse events (MAEs) were reported for either trial through 1 month. The 6-month primary patency for J-S, with PTA alone following atherectomy, was 40.4% (19/47). The 6-month primary patency for J-SII, with DCB treatment following atherectomy, was 96.7% (29/30). At 6-month post-procedure, 79.2% (38/48) of patients in J-S, and 100% (30/30) of patients in J-SII had improved by at least 1 Rutherford category., Conclusion: J-SUPREME trial results demonstrate procedural safety and efficacy of the Jetstream Atherectomy System and J-SII showed sustained patency through 6 months following combination treatment with Jetstream atherectomy and DCB.

Low serum albumin (SA) on admission in patients with acute myocardial infarction (AMI) has been reported to be associated with adverse cardiovascular events. The relation between low SA and post-AMI bleeding events is presently unknown. We analyzed 1,724 patients with AMI enrolled in the HAGAKURE-ACS registry who underwent primary percutaneous coronary intervention from January 2014 to December 2018. To assess the influence of low SA at admission, patients were divided into 3 groups according to the albumin tertiles: the low SA group (<3.8 g/100 ml), the middle SA (MSA) group (3.8 to 4.1 g/100 ml), and the normal SA (NSA) group (≥4.2 g/100 ml). The primary end point was the incidence of Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries moderate/severe bleeding. The cumulative 3-year incidence of the primary end point was significantly higher in the low SA group than in the MSA and NSA groups (30.8% and 11.9% vs 7.7%; p <0.001). In the landmark analysis at 30 days, the cumulative incidences of the primary end point were also significantly higher in the low SA group than in the MSA and NSA groups, both within and beyond 30 days (20.1% and 6.1% vs 3.5%; p <0.001, and 12.4% and 6.2% vs 4.5%; p <0.001, respectively). After adjusting for confounders, the low SA group showed excess risk of bleeding events relative to NSA (hazard ratio 1.56; 95% confidence interval 1.06 to 2.30; p = 0.026), whereas risk of bleeding was neutral in MSA relative to NSA (hazard ratio 0.94; 95% confidence interval 0.63 to 1.34; p = 0.752). In conclusion, low SA at admission was independently associated with higher risk for bleeding events in patients with AMI undergoing percutaneous coronary intervention., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The endoparasitic dinoflagellates belonging to the genus Amoebophrya can infect a broad range of free-living marine dinoflagellates, including harmful/toxic species. The parasite kills its host; the high prevalence of the parasite has been suggested to be a significant factor for the termination of dinoflagellate blooms in marine systems. The issues involved in culturing host-parasite systems have greatly restricted further research on Amoebophrya biology. Here, we established the culture of a novel strain of Amoebophrya sp. ex Alexandrium catenella (Group I) from Osaka Bay, Japan, and studied its genetic diversity, host specificity, and prevalence in the field. Genetic analysis established that the strain we isolated was a novel culture strain infecting A. catenella. Among the host species tested, the Amoebophrya sp. could infect the genera Alexandrium and Prorocentrum in culture, and the infection was also confirmed in the genus Tripos in a field sample. A maximum prevalence of 73% was recorded during the Alexandrium bloom period in Osaka Bay, after which the host cell density rapidly declined. Our results indicated that the existence of the parasite had a significant effect on the dynamics of A. catenella, especially on the termination of the blooms., (Copyright © 2021. Published by Elsevier B.V.)

An 86-year-old woman was admitted to our hospital with anemia. She had never experienced symptoms of serositis. Colonoscopy revealed colitis with erosions and a friable mucosa. First, she was diagnosed with unclassified inflammatory bowel disease (IBD-U). We suspected familial Mediterranean fever as a differential diagnosis of IBD-U, and MEFV gene analysis showed heterozygosity for Exon2 R202Q. The patient was treated with colchicine 0.5 mg. After 4 months, a follow-up colonoscopy showed remarkable improvement of the mucosal inflammation throughout the entire colon. MEFV gene-associated enterocolitis responding to colchicine may be observed in patients with IBD-U and elucidating the role of MEFV gene mutations in intestinal inflammation is a future challenge., (© 2021. Japanese Society of Gastroenterology.)

Objective: To assess the epidemiologic association between Kawasaki disease and common pediatric infectious diseases (PIDs) identified during the coronavirus disease 2019 (COVID-19) pandemic period to confirm whether the infection-triggered theory is a plausible hypothesis for the pathogenesis of Kawasaki disease., Study Design: A retrospective epidemiologic study was conducted using datasets obtained from Web-based surveillance of Kawasaki disease and PIDs in Japan. We compared weekly numbers of patients who developed Kawasaki disease and specific PIDs between 2020 and 2017-2019 and evaluated the association between the percent reduction in the number of patients with these diseases., Results: A total of 868 patients developed Kawasaki disease in 2020. During the social distancing period in 2020, the number of patients with Kawasaki disease was approximately 35% lower than in 2017-2019. Time from the onset of Kawasaki disease until the first hospital visit did not differ significantly among the examined years. The proportion of older children with Kawasaki disease decreased more than that of infants with Kawasaki disease (age <1 year), resulting in a significant difference in the proportion of infant patients between 2020 and 2017-2019 (24% vs 19%; P < .01). The number of patients with incomplete Kawasaki disease was unchanged from that of previous years. The weekly percent reduction in patient numbers differed between Kawasaki disease and PIDs during 2020, with no strong correlation between the 2 diseases., Conclusions: Our data indicate that parents of patients with Kawasaki disease did not avoid hospital visits during the COVID-19 pandemic period. The findings indicate the possibility that triggering Kawasaki disease might be associated with presently unidentified respiratory pathogen(s) that potentially might be acquired from both within and outside the household., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: We examined the trend in the number of missing teeth in a Japanese community over a 10-year period and the potential associated explanatory factors., Design: Prospective cohort study., Setting: A population-based study conducted in 2007, 2012 and 2017 in Japan (Hisayama Study)., Participants: Residents of a Japanese community aged 40-79 years undergoing dental examination in 2007 (n=2665), 2012 (n=2325) and 2017 (n=2285)., Outcome Measures: The number of missing teeth, periodontal condition, dental caries experience, dental plaque index and oral health behaviours were evaluated each year. The longitudinal analysis of variation in these factors were assessed using mixed models., Results: The age-adjusted and sex-adjusted mean number of missing teeth decreased with time (6.80 in 2007, 6.01 in 2012 and 4.99 in 2017). The mean clinical attachment level (CAL), prevalence of periodontitis and dental plaque index decreased over the study period, while dental caries experience slightly increased. The level of oral health behaviour increased over time. Poisson mixed models showed that changes in mean CAL and dental caries experience were positively associated with the change in the number of missing teeth over time. Linear mixed models showed that changes in dental plaque index and no regular dental visit were positively associated with changes in mean CAL., Conclusions: These findings suggest that a decreasing trend regarding the number of missing teeth in Japan might be associated with improvements in the periodontal condition due to changes in oral hygiene level and oral health behaviour., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In the modern US cardiovascular intensive care unit (CICU), the incidence of non-cardiovascular disorders has increased and non-cardiovascular disorders are associated with an increase in morbidity and mortality. In Japan, however, data regarding the association between non-cardiovascular disorders and outcomes in the CICU are limited., Methods: This study examined 490 consecutive admissions to a closed CICU at the Nippon Medical School Hospital from January to December 2017. Characteristics, diagnoses, treatments, and outcomes of admitted patients were identified., Results: The most common primary diagnosis was acute coronary syndrome (50.4%), followed by acute heart failure (20.0%), arrhythmia (6.7%), and non-cardiovascular diseases (3.7%). The mortality rate and median length of stay (LOS) in the CICU were 4.7% and 4 (interquartile range, 2-8) days, respectively. Of all patients, 42.2% (n = 207) developed non-cardiovascular complications such as acute respiratory failure, acute kidney injury, or sepsis during CICU stay. Multivariate logistic regression analysis revealed that acute respiratory failure and sepsis were significantly associated with mortality in the CICU (odds ratio, 11.014 and 25.678, respectively; both p<0.05). The multiple linear regression analysis showed that acute kidney injury was significantly associated with LOS in the CICU (β=0.144, p = 0.002)., Conclusions: Approximately half of patients admitted to the CICU had non-cardiovascular disorders including non-cardiovascular disease and non-cardiovascular complications, which were significantly associated with mortality and LOS in the CICU., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: The pandemic of a novel coronavirus disease 2019 (COVID-19) caused by a severe acute respiratory coronavirus 2 (SARS-CoV-2) infection has been problematic worldwide. A new SARS-CoV-2 antigen test (LUMIPULSE Ⓡ ) was licensed and widely used in Japan since May 2020. We conducted this study intending to whether the automated quantitative CLEIA antigen test using a saliva sample is effective and valid for the diagnosis of COVID-19., Patients and Methods: We analyzed and compared the diagnostic accuracy of both the automated quantitative CLEIA antigen test and real-time RT-PCR (rRT-PCR) using a saliva sample from individuals suspected as having COVID-19., Results: A total of 305 samples were collected and tested in Aichi Medical University Hospital and affiliated facilities from December 2020 until January 2021 at our institute. Using reverse-transcription PCR as a reference, the AUROC of the automated quantitative CLEIA antigen test was 0.903 (95% confidential interval 0.845-0.962, p < 0.001). The appropriate cut-off antigen level was 4.0 pg/mL and had a sensitivity of 77.8%, a specificity of 99.6%, a positive predictive value of 98%, and a negative predictive value of 94.5%. On the other hand, the diagnostic accuracy of the antigen test decreased among patients among patients with COVID-19 with threshold cycle (Ct-value)≥27, which shows the AUROC was 0.795 (95%CI 0.687-0.907, p < 0.001)., Conclusion: While the automated quantitative CLEIA antigen test from saliva specimen could be one of the most useful diagnostic tests for the diagnosis of COVID-19 in general practice, clinicians should know the limitations of the antigen test., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The Japanese Respiratory Society (JRS) has recommended spirometry for the diagnosis of respiratory diseases. It is indispensable for the confirmation of airflow obstruction by spirometry in chronic obstructive pulmonary disease (COPD) diagnosis. However, the coronavirus disease 2019 (COVID-19) pandemic has made it difficult for many clinics to perform spirometry as it may lead to possible aerosol infections. Thus, the diagnosis of COPD, especially in the early stage, has become difficult. To overcome this situation, JRS issued a "Flowchart of Working Diagnosis and Management of COPD during the COVID-19 Pandemic". This flowchart may help physicians provisionally diagnose COPD patients without performing spirometry, offering them appropriate intervention even in epidemic and pandemic situations., Competing Interests: Conflict of Interest Yoko Shibata: Lecture fees; GSK Japan, Boehringer Ingelheim Japan, AstraZeneca Japan, and Novartis Japan. Advisory Board: GSK Japan. Shigeo Muro: Honorarium from Boehringer Ingelheim Japan, AstraZeneca Japan, and Novartis Japan. Advisory Board: GSK Japan and AstraZeneca Japan. Akihito Yokoyama: Honorarium from Boehringer Ingelheim Japan, AstraZeneca Japan, GSK Japan, Sanofi Japan, and Novartis Japan. Shu Hashimoto: Lecture fees; AstraZeneca Japan, Boehringer Ingelheim Japan., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Long-term clinical outcomes among patients with cardiogenic shock (CS) and heart failure (HF) who survive the early phase of acute myocardial infarction (AMI) remain uncertain. We investigated 3283 consecutive patients with AMI, selected from a prospective, nation-wide multicenter registry (J-MINUET) database comprising 28 institutions in Japan between July 2012 and March 2014. The 3263 eligible patients were divided into the following three groups: CS-/HF- group (n = 2467, 75.6%); CS-/HF+ group (n = 479, 14.7%); and CS+ group (n = 317, 9.7%). The thirty-day mortality rate in CS+ patients was 32.8%, significantly higher than in CS- patients. Among CS+ patients, multivariate logistic regression analysis identified statin use before admission (Odds ratio (OR) 0.32, 95% confidence interval (CI) 0.14-0.66, P = 0.002), renal deficiency (OR 8.72, 95%CI 2.81-38.67, P < 0.0001) and final thrombolysis in myocardial infarction flow grade (OR 0.42, 95%CI 0.18-0.99, P = 0.046) were associated with 30-day mortality. Landmark Kaplan-Meier analysis showed that mortality rates after 30 days were comparable between CS+ and CS-/HF+ groups but were lower in the CS-/HF- group. Multivariate Cox hazard analysis also showed that hazard risk of mortality after 30 days was comparable between the CS+ and CS-/HF+ groups (Hazard ratio (HR) 1.03, 95%CI 0.63-1.68, P = 0.90), and significantly lower in the CS-/HF- group (HR 0.44, 95%CI 0.32-059, P < 0.0001). In conclusion, AMI patients with CS who survived 30 days experienced worse long-term outcomes compared with those without CS up to 3 years. Attention is required for patients who show HF on admission without CS to improve long-term AMI outcomes.

Background: Intravascular lithotripsy (IVL) delivers acoustic pressure waves to modify calcium, enhance vessel compliance and optimize stent deployment. The objective of this study was to assess the safety and effectiveness of IVL treatment of de novo stenoses involving severely calcified coronary vessels in a Japanese population., Methods and results: Disrupt CAD IV (NCT04151628) was a prospective, multicenter study designed for Japanese regulatory approval of coronary IVL (SWM-1234). The primary safety endpoint was freedom from major adverse cardiac events (MACE) at 30 days. The primary effectiveness endpoint was procedural success (residual stenosis <50% by QCA without in-hospital MACE). Noninferiority analyses for the primary endpoints were performed by comparing the CAD IV cohort with a propensity-matched historical IVL control group. Patients (intent-to-treat, n=64) were enrolled from 8 centers in Japan. Severe calcification by core laboratory assessment was present in all lesions, with a calcified length of 49.8±15.5 mm and a calcium angle of 257.9±78.4° by optical coherence tomography. Primary endpoints were achieved with non-inferiority demonstrated for freedom from 30-day MACE (CAD IV: 93.8% vs. Control: 91.2%, P=0.008), and procedural success (CAD IV: 93.8% vs. Control: 91.6%, P=0.007). No perforations, abrupt closures, or slow/no-reflow events occurred at any time during the procedures., Conclusions: Coronary IVL demonstrated high procedural success with low MACE rates in severely calcified lesions in a Japanese population.

Cough and sputum are common complaints at outpatient visits. In this digest version, we provide a general overview of these two symptoms and discuss the management of acute (up to three weeks) and prolonged/chronic cough (longer than three weeks). Flowcharts are provided, along with a step-by-step explanation of their diagnosis and management. Most cases of acute cough are due to an infection. In chronic respiratory illness, a cough could be a symptom of a respiratory infection such as pulmonary tuberculosis, malignancy such as a pulmonary tumor, asthma, chronic obstructive pulmonary disease, chronic bronchitis, bronchiectasis, drug-induced lung injury, heart failure, nasal sinus disease, sinobronchial syndrome, eosinophilic sinusitis, cough variant asthma (CVA), atopic cough, chronic laryngeal allergy, gastroesophageal reflux (GER), and post-infectious cough. Antibiotics should not be prescribed for over-peak cough but can be considered for atypical infections. The exploration of a single/major cause is recommended for persistent/chronic cough. When sputum is present, a sputum smear/culture (general bacteria, mycobacteria), cytology, cell differentiation, chest computed tomography (CT), and sinus X-ray or CT should be performed. There are two types of rhinosinusitis. Conventional sinusitis and eosinophilic rhinosinusitis present primarily with neutrophilic inflammation and eosinophilic inflammation, respectively. The most common causes of dry cough include CVA, atopic cough/laryngeal allergy (chronic), GER, and post-infectious cough. In the last chapter, future challenges and perspectives are discussed. We hope that the clarification of the pathology of cough hypersensitivity syndrome will lead to further development of "pathology-specific non-specific therapeutic drugs" and provide benefits to patients with chronic refractory cough., Competing Interests: Conflict of Interest Dr. Hiroshi Mukae received honoraria from Daiichi Sankyo Co., Ltd., Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., KYOLIN Pharmaceutical Co., Ltd., Pfizer Japan Inc., MSD K.K., Taisho Pharma Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Astellas Pharma Inc., and AstraZeneca K.K., a research grant from Nippon Boehringer Ingelheim Co., Ltd., and subsidies or donations from Fujifilm Toyama Chemical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Ltd., Taisho Pharma Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Astellas Pharma Inc., KYORIN Pharmaceutical Co., Ltd., and Shionogi & Co., Ltd.; Dr. Takeshi Kaneko received honoraria from Pfizer Japan Inc., KYORIN Pharmaceutical Co., Ltd., GlaxoSmithKline K.K., AstraZeneca K.K., Novartis Pharma K.K., Nippon Boehringer Ingelheim Co., Ltd., and Meiji Seika Pharma Co., Ltd., and a research grant from Teijin Home Healthcare Ltd., Ono Pharmaceutical Co., Ltd., and Taiho Pharmaceutical Co., Ltd.; Dr. Toshio Katsunuma received honoraria from KYORIN Pharmaceutical Co., Ltd., Maruho Co., Ltd. and Torii Pharmaceutical Co., Ltd.; Dr. Akio Niimi received honoraria from AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., MSD K.K., KYORIN Pharmaceutical Co., Ltd., GlaxoSmithKline K.K. and Novartis Pharma K.K., a research grant from Novartis Pharma K.K., Boston Scientific Corporation, MSD K.K., and Nippon Boehringer Ingelheim Co., Ltd., and subsidies or donations from Nippon Boehringer Ingelheim Co., Ltd., KYORIN Pharmaceutical Co., Ltd. and Ono Pharmaceutical Co., Ltd.; Dr. Hiroto Matsuse received honoraria from MSD K.K., AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., Pfizer Japan Inc., KYORIN Pharmaceutical Co., Ltd., and Astellas Pharma Inc.; Dr. Kazuhiro Yatera received honoraria from AstraZeneca K.K., Novartis Pharma K.K., Nippon Boehringer lngelheim Co., Ltd., Astellas Pharma Inc., GlaxoSmithKline K.K., and KYORIN Pharmaceutical Co., Ltd., and subsidies or donations from Kirigaoka Tsuda Hospital, Tochiku Hospital, Hagiwara Central Hospital, Kurate Hospital, Shionogi & Co., Ltd., Teijin Home Healthcare Ltd., Taiho Pharmaceutical Co., Ltd., MSD K.K., Novartis Pharma K.K., and Nippon Boehringer Ingelheim Co., Ltd.; Dr. Arata Azuma received honoraria from Nippon Boehringer Ingelheim Co., Ltd.; Dr. Hirokazu Arakawa received subsidies or donations from Novartis Pharma K.K.; Dr. Takashi Iwanaga received honoraria from KYORIN Pharmaceutical Co., Ltd., a research grant from KYORIN Pharmaceutical Co., Ltd., Pearl Therapeutics, Inc., and Meiji Seika Pharma Co., Ltd., and subsidies or donations from Nippon Boehringer Ingelheim Co., Ltd., Astellas Pharma Inc., Teijin Pharma Ltd., and KYORIN Pharmaceutical Co., Ltd.; Dr. Yasuhiro Gon received honoraria from Novartis Pharma K.K., AstraZeneca K.K., GlaxoSmithKline K.K., Nippon Boehringer Ingelheim Co., Ltd., and KYORIN Pharmaceutical Co., Ltd., and a research grant from Novartis Pharma K.K. and AstraZeneca K.K.; Dr. Hirokazu Sakamoto received a research grant from Sanofi K.K. and Novartis Pharma K.K.; Dr. Yoko Shibata received honoraria from AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., and GlaxoSmithKlein K.K.; Dr. Tsutomu Tamada serves as a consultant to Novartis Pharma K.K. and AstraZeneca K.K.; Dr. Yasuhiko Nishioka received honoraria from Nippon Boehringer lngelheim Co., Ltd., Chugai Pharmaceutical Co., Ltd., and MSD K.K., a research grant from Taiho Pharmaceutical Co., Ltd., Nippon Boehringer lngelheim Co., Ltd., Chugai Pharmaceutical Co., Ltd., and Bonac Corporation, and subsidies or donations from Ono Pharmaceutical Co., Ltd., Nippon Boehringer lngelheim Co., Ltd., Taiho Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Asahi Kasei Pharma Corporation, and Chugai Pharmaceutical Co., Ltd.; Dr. Shigeharu Fujieda received patent royalties and/or licensing fees from KYORIN Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, and Taiho Pharmaceutical Co., Ltd., and a research grant from Mitsubishi Tanabe Pharma Corporation, Tsumura Co., Ltd., Maruho Co., Ltd., and Sanofi K.K.; Dr. Naoyuki Miyashita received honoraria from Daiichi Sankyo Co., Ltd., AstraZeneca K.K., Astellas Pharma Inc., Pfizer Japan Inc., and Taisho Toyama Pharmaceutical Co., Ltd.; Dr. Akihito Yokoyama received honoraria from AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., GlaxoSmithKlein K.K., and Sanofi K.K., and a research grant from Astellas Pharma Inc. and Ono Pharmaceutical Co., Ltd. Drs. Yasushi Obase, Masaharu Shinkai, Kiyoshi Takeyama, Jiro Terada, Yoshihiro Yamamoto, Haruhiko Ogawa, Kiyoyasu Kurahashi, Shusaku Haranaga, Hiroyuki Mochizuki, Shigemi Yoshihara, and Jun Tamaoki have no conflict of interest.Drs. Yasushi Obase, Masaharu Shinkai, Kiyoshi Takeyama, Jiro Terada, Yoshihiro Yamamoto, Haruhiko Ogawa, Kiyoyasu Kurahashi, Shusaku Haranaga, Hiroyuki Mochizuki, Shigemi Yoshihara, and Jun Tamaoki have no conflict of interest., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Comprehensive cancer genomic profiling has been used recently for patients with advanced solid cancers. Two cancer genomic profiling tests for patients with no standard treatment are covered by Japanese public health insurance since June 2019., Methods: We prospectively analyzed data of 189 patients with solid cancers who underwent either of the two-cancer genomic profiling tests at Hokkaido University Hospital and its liaison hospitals and whose results were discussed in molecular tumor board at Hokkaido University Hospital between August 2019 and July 2020., Results: All 189 patients had appropriate results. Actionable gene alterations were identified in 93 patients (49%). Frequent mutations included PIK3CA (12%) mutation, BRCA1/2 alteration (7%), ERBB2 amplification (6%) and tumor mutation burden-High (4%). The median turnaround time from sample shipping to acquisition by the expert panel was 26 days. Although 115 patients (61%) were provided with information for genotype-matched therapies, only 21 (11%) received them. Notably, four of eight patients below the age of 20 years were provided information for genotype-matched therapies, and three received them. Their response rates and disease control rates were 29% and 67%, respectively. Most patients who did not undergo the genotype-matched therapies were provided information for only investigational drugs in phases I and II at distant clinical trial sites in central Japan. Twenty-six patients were informed of suspected germline findings, while 11 patients (42%) received genetic counseling., Conclusions: The publicly reimbursed cancer genomic profilings may lead to the modest but favorable therapeutic efficacy of genotype-matched therapy for solid cancer patients with no standard therapy. However, poor access to genotype-matched therapy needs to be resolved., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Small cell lung cancer(SCLC)is one of the histological types of lung cancer showing the worst prognosis, and is often diagnosed as an inoperable advanced stage disease. Recently, several comprehensive genomic analyses for SCLC have shown that inactivating mutations of tumor suppressor genes such as TP53 and RB1 and MYC family gene amplifications are involved in the development and progression of SCLC. However, actionable gene alterations for targeted therapies have not yet been identified, and there has been no significant advance in the development of targeted therapies for SCLC. In a nationwide lung cancer genome screening project in Japan, LC‒SCRUM‒Japan, a large‒scale genomic analysis was prospectively performed for Japanese SCLC patients, and based on this genomic analysis, a clinical study to evaluate the efficacy of a targeted therapy for PI3K/AKT/mTOR pathway gene‒altered SCLC(EAGLE‒PAT trial)was conducted. In this article, we describe the results of the genomic analysis in LC‒SCRUM‒Japan and the EAGLE‒PAT trial, and also provide the overview of genetic alterations reported in SCLC and the current and future development of targeted therapies for SCLC.

We aimed to determine whether puncture sites for blood sampling and topical disinfectants are associated with rates of contaminated blood cultures in the emergency department (ED) of a single institution. This single-center, prospective observational study of 249 consecutive patients aged ≥ 20 years proceeded in the ED of a university hospital in Japan during 6 months. Pairs of blood samples were collected for aerobic and anaerobic culture from all patients in the ED. Physicians selected puncture sites and topical disinfectants according to their personal preference. We found 50 (20.1%) patients with potentially contaminated blood cultures. Fifty-six (22.5%) patients were true bacteremia and 143 (57.4%) patients were true negatives. Multivariate analysis associated more frequent contamination when puncture sites were disinfected with povidone-iodine than with alcohol/chlorhexidine (adjusted risk difference, 12.9%; 95% confidence interval [CI] 8.8-16.9; P < 0.001). Sites of blood collection were also associated with contamination. Femoral and central venous with other sites were associated with contamination more frequently than venous sites (adjusted risk difference), 13.1% (95% CI 8.2-17.9; P < 0.001]) vs. 17.3% (95% CI 3.6-31.0; P = 0.013). Rates of contaminated blood cultures were significantly higher when blood was collected from femoral sites and when povidone-iodine was the topical antiseptic.

Although gender difference in long-term outcomes after acute myocardial infarction have been shown previously, impact of age on gender difference is still controversial. This study focused on the association between age and gender difference in long-term outcome. We analyzed data from 3,283 consecutive patients who were included in a prospective, nationwide, multicenter registry (Japan Registry of Acute Myocardial Infarction Diagnosed by Universal Definition) from 2012 to 2014. The primary end point was the major adverse cardiovascular event (MACE), which was defined as a composite of death, myocardial infarction, stroke, heart failure, and revascularization for unstable angina during 3 years. Patients were divided into 4 strata according to age: those with age <65 years (group 1: n = 1161), 65 to 74 years (group 2: n = 954), 75 to 84 years (group 3: n = 866) and 84< years (group 4: n = 302). Although the crude incidence of 3-year MACE was significantly higher in women than men (36.4% vs. 28.5%, p <0.001), there was not significant gender difference in each group (group 1, 19.6% vs 19.0%, p = 0.74; group 2, 33.1% vs 28.3%, p = 0.25; group 3, 38.9% vs 39.6%, p = 0.54; and group 4, 54.0% vs 56.8%, p = 0.24). In conclusion, although women had higher crude incidence of 3-year MACE than men, there was no gender difference in each group., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: In April 2008, the guidelines for obstetric practice in Japan have made the following recommendations: (1) do not use vacuum extraction (VE) for more than 20 min, and consider forceps delivery (FD) or an emergency cesarean section (CS) if necessary (20-minute VE trial rule), and (2) do not try VE more than five times, even if VE has been used for less than 20 min (5-time VE trial rule). The aims of the present study were to compare the obstetric policies related to failed VE before and after 2008. Methods: We reviewed the obstetric records of all cases of VE in cases of singleton pregnancy with a neonatal birth weight ≥ 2500 g beyond 37 weeks' gestation at our hospital from April 2002 to March 2014. Results: The success rate of VE decreased significantly (96.8 versus 94.1%, p  = .02), while the rate of CS increased significantly (2.2 versus 5.0%, p  < .01); however, there were no significant differences in these values between the two periods. Conclusions: We could not find the effects of the recommendation limiting the practice of VE.

Background/aim: There are several treatment options for metastatic hormone-sensitive prostate cancer (mHSPC) in the world. In recent years, the use of docetaxel, abiraterone, enzalutamide, and apalutamide has been used for mHSPC, but combined androgen blockade (CAB) therapy using first-generation antiandrogens has been widely used in Japan. There is a background. We performed a consecutive study of patients who received combined androgen blockade (CAB) at a single institute to determine the prognostic factors for mHSPC., Patients and Methods: We conducted a consecutive study of 237 mHSPC patients treated with CAB from 2003 to 2017 at the Gunma University Hospital. Prostate-specific antigen progression-free survival (PSA-PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. The associations between pre-treatment risk factors and the PSA response 3 months after starting CAB, PSA-PFS, and OS were evaluated by the Cox proportional hazards model., Results: Among the 237 cases, the median PSA-PFS and OS times were 63.0 and 91.4 months, respectively. The median PSA-PFS and OS times of M1 cases (174 cases, 73.4% of all 237 cases) were 36.1 and 75.9 months, respectively. The Eastern Cooperative Oncology Group performance status (ECOG PS) score, hemoglobin (Hb), lactate dehydrogenase, extent of disease, visceral metastasis (no vs. yes), and PSA response after 3 months were significant predictors of OS according to Cox regression analysis of prognostic factors in M1 patients. The ECOG PS, Hb, visceral metastasis (no vs. yes), and PSA response after 3 months predicted OS high-risk patients in LATITUDE criteria. The OS was 92.1 months in the low-risk group (0-1 risk factors), 48.2 months in the intermediate-risk group (2 risk factors), and 16.9 months in the high-risk group (3-4 risk factors)., Conclusion: CAB should be considered as a treatment option for strictly selected patients with mHSPC, even though novel treatments are available., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Optimization of medication therapy for the elderly is a matter of rapidly growing importance, which is addressed by pharmacists through comprehensive reviews. In this study, the impact of medication review by pharmacists on medication optimization and avoidance of adverse drug events (ADE) was investigated, as well as differences in the triggers for pharmaceutical intervention to allow for optimization of medication by patient age. Data for this study were collected from reports recorded between April 2013 and March 2019 for patients admitted to the Hiroshima University Hospital. In response to pharmacists' proposals, prescriptions were modified in 18932 cases, comprising 17% of the total 111479 patients during hospitalization. The frequency of such intervention was higher in elderly patients aged ≥65 years than in those <65 years (20 vs. 14%, p < 0.01). The reasons for pharmacists' intervention were primarily (67%) medication history or clinical symptoms in all age groups. Patient complaint was a minor reason in patients aged ≥75 years, accounting for only 2% of all interventions; laboratory results were a more typical reason, accounting for 24% of all interventions. These findings reveal the importance of pharmacists' interventions for optimizing medication and preventing ADEs, particularly in elderly patients. Thus, pharmacists must evaluate the medications and conditions, including laboratory results, in the medical records of elderly patients more carefully than those of younger patients as elderly patients might be unable to communicate about subjective symptoms.

More than fifty cultivated varieties of blueberries are grown under the same processing conditions on the farm at Chiba Prefectural Agricultural College in Japan. The fruits from 51 blueberry cultivars, including 16 rabbiteye (RE) cultivars (Vaccinium ashei Reade) and 35 highbush (HB) cultivars (Vaccinium corybosum L.), were evaluated for total anthocyanin contents, phenolic contents, and their contribution to antioxidant activity among cultivars. Total anthocyanin contents varied from 0.74±0.21 ("Barkley") to 4.27±0.18 ("Suwannee") mg as cyanidin-3-glucoside (Cy-3-GC) equivalent/g fresh-weight (fw), with phenolic contents in the range of 0.77±0.14 ("Floridablue") to 3.69±0.89 ("Suwannee") mg of gallic acid equivalent (GAE)/g fw, which strongly correlated with antioxidant activities assessed using the DPPH and ORAC methods, respectively. Total anthocyanin and phenolic contents were both significantly higher (p<0.05) in RE blueberries than in HB blueberries. Furthermore, the total phenolic values were significantly higher for the RE family than for the HB family (p<0.01). In comparisons of two species, the major anthocyanidin identified were malvidin in RE blueberries and delphinidin in HB blueberries. This result suggests that some RE blueberries, especially "Suwannee," "Homebell" and "Climax," are suitable supply sources with high in vitro antioxidant capacity. This study would be helpful to the quality-oriented cultivation of blueberry.

The prognostic impact of transfer to another hospital among acute heart failure (AHF) patients has not been well elucidated.Of the 800 AHF patients analyzed, 682 patients were enrolled in this study for analysis. The subjects were divided into two groups according to their discharge location: discharge home (Group-H, n = 589) or transfer to another hospital for rehabilitation (Group-T, n = 93). The Kaplan-Meier curves revealed a poorer prognosis, including all-cause death and heart failure (HF) events (death, readmission-HF), in Group-T than that in Group-H (P < 0.001, respectively). A multivariate Cox regression model showed that Group-T was an independent predictor of 365-day all-cause death (hazard ratio: 2.618, 95% confidence interval [CI]: 1.510-4.538, P = 0.001). The multivariate logistic regression analysis showed that aging (per 1-year-old increase, odds ratio [OR]: 1.056, 95% CI: 1.028-1.085, P < 0.001), female gender (OR: 2.128, 95% CI: 1.287-3.521, P = 0.003), endotracheal intubation during hospitalization (OR: 2.074, 95% CI: 1.093-3.936, P = 0.026), and increased Controlling Nutritional Status score on admission (per 1.0-point increase, OR: 1.247, 95% CI: 1.131-1.475, P < 0.001) were associated with transfer to another hospital after AHF admission. The prognosis, including all-cause death, was determined to be significantly poorer in patients who were transferred to another hospital, as their activities of daily living were noted to lessen before discharge (n = 11) compared to others (n = 82).Elderly AHF patients suffering from malnutrition were difficult to discharge home after AHF admission, and transfer to another hospital only led to adverse outcomes. Appropriate rehabilitation during definitive hospitalization appears necessary for managing elderly patients in the HF pandemic era.

The impact of elevated total bilirubin (Tbil) levels on adverse clinical outcomes in patients with acute heart failure (HF) has not been fully established, although liver damage is common among these patients. We therefore examined the associations between Tbil levels at admission and systolic blood pressure (SBP) in patients with acute HF in an emergency setting and to evaluate clinical outcomes related to elevated Tbil, particularly in patients with SBP < 100 mmHg. Clinical data and outcomes in acute HF patients (n = 877) were compared according to Tbil quartiles. SBP values < 100 mmHg were more prevalent among patients in the highest quartile (Tbil ≥ 1.0 mg/dL) vs. others (15.4% vs. 3.1%, p < 0.001). Tbil levels were inversely and significantly correlated with SBP at admission (Spearman's ρ, - 0.243; p < 0.001). Kaplan-Meier estimate survival curves showed that event-free survival was worse among patients in the highest Tbil quartile vs. others (78.5% vs. 90.4%, p < 0.001). When comparing survival rates among patients in SBP < 100 mmHg (n = 50), the difference of survival rate became larger for the patients in the highest quartile (n = 29) vs. others (n = 21) (41.4% vs. 77.7%, p < 0.001). Multivariate Cox proportional hazard analysis showed that Tbil ≥ 1.3 mg/dL, not SBP or B-type natriuretic peptide, independently and significantly predicted cardiac death within 180 days in acute HF patients with SBP < 100 mmHg (hazard ratio 3.74; 95% confidence interval 1.39-10.05; p < 0.001). In conclusion, Tbil levels were inversely correlated with SBP at admission in patients with acute HF. Tbil levels independently predicted the risk of 180-day cardiac mortality, especially in acute HF patients with SBP < 100 mmHg.

Rotational atherectomy (RA) has been widely used for percutaneous coronary intervention (PCI) to severely calcified lesions. As compared to other countries, RA in Japan has uniquely developed with the aid of greater usage of intravascular imaging devices such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT). IVUS has been used to understand the guidewire bias and to decide appropriate burr sizes during RA, whereas OCT can also provide the thickness of calcification. Owing to such abundant experiences, Japanese RA operators modified RA techniques and reported unique evidences regarding RA. The Task Force on Rotational Atherectomy of the J apanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has now proposed the expert consensus document to summarize the contemporary techniques and evidences regarding RA.

Background: To establish an individualized surgical strategy for lymphadenectomy in ovarian cancer patients with the germline BRCA1 and BRCA2 pathogenic variants (BRCA1+ and BRCA2+), we investigated the clinicopathological characteristics that are involved in the increased risk of lymph node metastasis., Methods: We retrospectively reviewed the data of Japanese women registered in the database of the Japanese Hereditary Breast and Ovarian Cancer Consortium, who underwent BRCA1 and BRCA2 genetic testing., Results: We evaluated the predictors of lymph node metastasis in all patients with the information of age at the diagnosis, disease site, histological subtype, 2014 FIGO stage, personal breast cancer history and family history; 233, 153 and 32 patients in the BRCA- (no pathogenic variant), BRCA1+ and BRCA2+ groups, respectively. The prevalence of lymph node metastasis was not markedly different between BRCA- (20.0%), BRCA1+ (18.4%) and BRCA2+ (26.2%). Multivariate analysis revealed an absence of a family history of ovarian cancer as an independent predictor for an increased risk of lymph node metastasis in BRCA1+, and the prevalence of lymph node metastasis was 11.7 and 42.0% in the groups with and without a family history of ovarian cancer, respectively. This subgroup without a family history of ovarian cancer did not show any correlation with a particular variant of BRCA1, including two common variants of c.188 T > A and c.2800C > T., Conclusions: This study suggested that certain genetic factors related to the penetrance of hereditary breast and ovarian cancer syndrome altered the frequency of lymph node metastasis in BRCA1+ ovarian cancer, and family history may be useful to personalize the indication of lymphadenectomy., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: The association between guideline adherence and long-term outcomes in patients with acute myocardial infarction in real-world clinical practice remains unclear., Methods: We investigated 3283 consecutive patients with acute myocardial infarction who were selected from a prospective, nation-wide, multicentre registry (J-MINUET) database covering 28 institutions in Japan between July 2012 and March 2014. Among the 2757 eligible patients, we evaluated the use of seven guideline-recommended therapies, including urgent revascularisation, door-to-balloon time of 90 minutes or less, and five discharge medications (P2Y12 inhibitors on aspirin, beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, statins, lipid-lowering drugs). The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, cardiac failure and urgent revascularisation for unstable angina up to 3 years., Results: The overall median composite guideline adherence was 85.7%. Patients were divided into the following three groups: complete (100%) adherence group ( n =862); moderate adherence (75% to <100%) group ( n =911); and low adherence (0-75%) group ( n =984). The rate of adverse cardiovascular events was significantly lower in the complete adherence group than in the low and moderate adherence groups (log rank P <0.0001). Multivariate Cox regression analysis showed complete guideline adherence was also significantly associated with lower adverse cardiovascular events compared with low guideline adherence (hazard ratio 0.66; 95% confidence interval 0.52-0.85; P =0.001)., Conclusion: The use of guideline-based therapies for patients with acute myocardial infarction in contemporary clinical practice was associated with significant decreases in adverse long-term clinical outcomes., Trial Registration: UMIN Unique trial Number: UMIN000010037.

Background: Patients with peripheral artery disease (PAD) are at high risk of cardiovascular events, including myocardial infarction (MI), stroke, and cardiovascular death. However, the impact of PAD on prognosis in Japanese patients with acute MI remains unclear., Methods: The Japanese registry of acute Myocardial INfarction diagnosed by Universal dEfiniTion (J-MINUET) is a prospective multicenter registry that registered 3283 patients with acute MI. Among them, 2970 patients with available data of PAD were divided into the following 4 groups: 2513 patients without prior MI or PAD (None group), 320 patients with only prior MI (Prior MI group), 100 patients with only PAD (PAD group), and 37 patients with both previous MI and PAD (Both group). The primary endpoint was a composite of all-cause death, non-fatal MI, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina., Results: The 3-year cumulative incidence of the primary endpoint was 26.9% in None group, 41.4% in Prior MI group, 48.0% in PAD group, and 60.3% in Both group (p < 0.001). In multivariate analysis, hazard ratio using None group as reference was 1.55 (95% confidence intervals 1.25-1.91; p < 0.001) for MI group, 2.26 (1.61-3.07; p < 0.001) for PAD group, and 2.52 (1.52-3.90; p < 0.001) for Both group., Conclusions: Concomitant PAD was associated with poor prognosis in Japanese patients with acute MI., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Although B-type natriuretic peptide (BNP) has gradually gained recognition as an indicator in risk stratification for patients with acute myocardial infarction (AMI), the prognostic impact on long-term clinical outcomes in patients with non-ST-segment elevation acute myocardial infarction (NSTEMI) without creatine kinase (CK) elevation remains unclear.This prospective multicenter study assessed 3,283 consecutive patients with AMI admitted to 28 institutions in Japan between 2012 and 2014. We analyzed 218 patients with NSTEMI without CK elevation (NSTEMI-CK) for whom BNP was available. In the NSTEMI-CK group, patients were assigned to high- and low-BNP groups according to BNP values (cut-off BNP, 100 pg/mL). The primary endpoint was defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina up to 3 years. Primary endpoints were observed in 60 (33.3%) events among patients with NSTEMI-CK. Kaplan-Meier analysis revealed a significantly higher event rate for primary endpoints among patients with high BNP (log-rank P < 0.001). After adjusting for covariates, a higher BNP level was significantly associated with long-term clinical outcomes in NSTEMI-CK (adjusted hazard ratio, 4.86; 95% confidence interval, 2.18-12.44; P < 0.001).The BNP concentration is associated with adverse long-term clinical outcomes among patients with NSTEMI-CK who are considered low risk. Careful clinical management may be warranted for secondary prevention in patients with NSTEMI-CK with high BNP levels.