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Robotic surgery is gaining traction in Japan due to its technological advancements, but its financial viability for hospitals remains uncertain. This study investigates the impact of robotic surgery on hospital gross profits, comparing it to laparoscopic surgery using data from surgeries performed at Red Cross Hospital Osaka. The study spans multiple surgical fields, including gastrointestinal, urology, gynecology, and thoracic surgery. While the number of robotic surgeries has increased, they consistently generate lower gross profits for hospitals compared with laparoscopic surgeries, primarily due to the high costs of robotic instruments and maintenance. Certain procedures, such as hernia repair, proximal gastrectomy, and distal pancreatectomy, result in negative profits when performed robotically. This article highlights the financial challenges hospitals face under Japan's current healthcare reimbursement system, where the fees for robotic and laparoscopic surgeries are largely the same. Policy adjustments may be necessary to ensure the financial sustainability of robotic surgery., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Glasdegib is a potent, selective, oral inhibitor of the hedgehog signaling pathway. In this phase I study, previously untreated Japanese patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes were treated with glasdegib (100 mg once daily) combinations: low-dose cytarabine (20 mg twice daily; cohort 1, n = 6; expansion cohort, n = 15); daunorubicin and cytarabine (60 mg/m 2 i.v.; cohort 2, n = 6); or azacitidine (100 mg/m 2 i.v.; cohort 3, n = 6). Patients, except cohort 2, were ineligible for intensive chemotherapy. The primary end-point was dose-limiting toxicity in cohorts 1-3 and disease-modifying response in the expansion cohort. Disease-modifying response rate was tested with the null hypothesis of 6.8%, which was set based on the results from the phase II BRIGHT AML 1003 study (NCT01546038). No dose-limiting toxicities were observed in cohorts 1 or 3; one patient in cohort 2 experienced a dose-limiting toxicity of grade 3 erythroderma. The most common grade ≥3 treatment-related adverse events were neutropenia and thrombocytopenia (66.7% each) in cohort 1 and thrombocytopenia (60.0%) in the expansion cohort. In the expansion cohort, the disease-modifying response rate was 46.7% (90% confidence interval, 24.4-70.0; p < 0.0001), with all patients achieving either a complete response or complete response with incomplete blood count recovery. Median overall survival was 13.9 months. In this study, the primary disease-modifying response end-point with glasdegib plus low-dose cytarabine was met. The study confirms the safety and efficacy of glasdegib plus low-dose cytarabine in Japanese patients with AML ineligible for intensive chemotherapy., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Purpose: The increased global burden of non-communicable diseases and mental disorders is an urgent health challenge for countries around the entire world, especially those experiencing super-ageing societies, where over 21% of the population is age 65 years or older. Japan is the world's most rapidly ageing society, and as a result, medical costs are also rising dramatically. With the aims of establishing a foundational framework for future research efforts, primarily focusing on the development of a personal health record (PHR) system, and creating a long-term repository for bioresources integrated with PHRs, this study investigated potential health risks and future healthcare burdens based on a longitudinal analysis of health records., Participants: The Resource Center for Health Science (RECHS) project is a long-term, prospective biobank project, population and health check-up-based cohort that primarily investigates the associations between lifestyle and environmental factors and some surrogate markers of non-communicable diseases, such as diabetes, hypertension, cardiovascular disease and cancer. Starting in 2010, we initiated an annual cohort study among voluntary participants recruited from health check-up programmes and collected data from the following sources: a self-administered baseline questionnaire that included items on dietary habits and stress, a Brief Self-Administered Diet History Questionnaire, the Centre for Epidemiologic Studies Depression Scale and the General Health Questionnaire-28., Findings to Date: For this prospective cohort study, we planned to enrol approximately 10 000 participants. We collected and stored serum samples from all participants for future analyses. The study participants who still were able to participate in these health check-ups and their outcomes were then obtained from the measurements and questionnaire responses., Future Plans: Insights emerging from the RECHS study can provide researchers and public health policy administrators with evidence to aid in the prevention of non-communicable diseases and clarify the most malleable status to implement preventive measures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, guidance ("Japanese Guide") has been published by a working group of several academic societies and announced by the Ministry of Health, Labour, and Welfare. Steroids as a candidate treatment for COVID-19 were noted in the Japanese Guide. However, the prescription details for steroids, and whether the Japanese Guide changed its clinical practice, were unclear. This study aimed to examine the impact of the Japanese Guide on the trends in the prescription of steroids for COVID-19 inpatients in Japan. We selected our study population using Diagnostic Procedure Combination (DPC) data from hospitals participating in the Quality Indicator/Improvement Project (QIP). The inclusion criteria were patients discharged from hospital between January 2020 and December 2020, who had been diagnosed with COVID-19, and were aged 18 years or older. The epidemiological characteristics of cases and the proportion of steroid prescriptions were described on a weekly basis. The same analysis was performed for subgroups classified by disease severity. The study population comprised 8603 cases (410 severe cases, 2231 moderate II cases, and 5962 moderate I/mild cases). The maximum proportion of cases prescribed with dexamethasone increased remarkably from 2.5 to 35.2% in the study population before and after week 29 (July 2020), when dexamethasone was included in the guidance. These increases were 7.7% to 58.7% in severe cases, 5.0% to 57.2% in moderate II cases, and 1.1% to 19.2% in moderate I/mild cases. Although the proportion of cases prescribed prednisolone and methylprednisolone decreased in moderate II and moderate I/mild cases, it remained high in severe cases. We showed the trends of steroid prescriptions in COVID-19 inpatients. The results showed that guidance can influence drug treatment provided during an emerging infectious disease pandemic., (© 2023. The Author(s).)

Next-generation sequencing of AML has identified specific genetic mutations in AML patients. Hematologic Malignancies (HM)-SCREEN-Japan 01 is a multicenter study to detect actionable mutations using paraffin-embedded bone marrow (BM) clot specimens rather than BM fluid in AML patients for whom standard treatment has not been established. The purpose of this study is to evaluate the presence of potentially therapeutic target gene mutations in patients with newly diagnosed unfit AML and relapsed/refractory AML (R/R-AML) using BM clot specimens. In this study, 188 patients were enrolled and targeted sequencing was undertaken on DNA from 437 genes and RNA from 265 genes. High-quality DNA and RNA were obtained using BM clot specimens, with genetic alterations successfully detected in 177 patients (97.3%), and fusion transcripts in 41 patients (23.2%). The median turnaround time was 13 days. In the detection of fusion genes, not only common fusion products such as RUNX1-RUX1T1 and KMT2A rearrangements, but also NUP98 rearrangements and rare fusion genes were observed. Among 177 patients (72 with unfit AML, 105 with R/R-AML), mutations in KIT and WT1 were independent factors for overall survival (hazard ratio = 12.6 and 8.88, respectively), and patients with high variant allele frequency (≥40%) of TP53 mutations had a poor prognosis. As for the detection of actionable mutations, 38% (n = 69) of patients had useful genetic mutation (FLT3-ITD/TKD, IDH1/2, and DNMT3A R822 ) for treatment selection. Comprehensive genomic profiling using paraffin-embedded BM clot specimens successfully identified leukemic-associated genes that can be used as therapeutic targets., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objective: Establishing appropriate percutaneous coronary intervention (PCI) in stable angina pectoris (SAP) has become a distinctive performance measure worldwide. Clinical guidelines call for documenting ischaemia in patients with SAP prior to elective PCI. The Japanese Ministry of Health, Labour and Welfare introduced a new reimbursement policy in April 2018 to promote the appropriate and judicious implementation of PCI. The 2018 reimbursement changes clarified the required proof of ischaemia. Tests to evaluate functional ischaemia and coronary stenosis have been added as a requirement for reimbursement. We examined whether this reimbursement revision had an impact on PCI procedures for SAP in Japan., Methods: We used administrative claims data in Japan's Diagnosis Procedure Combination database from April 2014 through March 2020. We used interrupted time series analyses with a control to ascertain the impacts on elective PCI procedures before and after the Japanese reimbursement revision. The primary outcome was the change in elective PCI procedures per month. Emergent PCI procedures served as a control group., Results: A total of 773 240 PCI procedures were identified between April 2014 and March 2020: 388 817 and 180 462 elective PCIs before and after the reimbursement revision, respectively. After the 2018 reimbursement revision, significant trend changes were found in elective PCI procedures per month (-106.3, 95% CI -155.8 to -56.8, p<0.01), while the number of emergent PCIs remained stable throughout the study period., Conclusions: After revising the reimbursement tariff for elective PCIs in 2018, there was a significant reduction in elective PCI procedures per month., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Declines in cardiovascular diseases during the first surge of coronavirus disease 2019 (COVID-19) have been reported. With the repeating surges of COVID-19, we aim to investigate the medium-term impact of the COVID-19 pandemic on the practice of percutaneous coronary interventions (PCIs)., Methods: We performed a descriptive analysis of rates of PCIs, utilizing administrative data in Japan. Changes in the proportion of severe cases and in-hospital mortality since the start of the COVID-19 pandemic were investigated using interrupted time series (ITS) analyses., Results: From April 2018 to February 2021, 38,696 and 28,585 cases of elective and emergency PCIs, respectively, were identified. The rates of PCIs decreased during the first and third COVID-19 surges. The ratios of monthly rates of elective PCIs to that in the corresponding months during the previous 2 years were 50.3% in May 2020 and 76.1% in January 2021. The decrease in rates of emergency PCIs was smaller than that of elective PCIs. The ITS analyses did not identify any significant changes in the proportion of severe cases and in-hospital mortality., Conclusions: We found that the impacts of COVID-19 on PCIs were larger in the first surge than in the subsequent and larger in the elective than in the emergency; this continued over the medium-term. During the COVID-19 pandemic, in-hospital mortality of cases undertaking emergency PCIs did not change.

Background: Maintaining critical care for non-Coronavirus-disease-2019 (non-COVID-19) patients is a key pillar of tackling the impact of the COVID-19 pandemic. This study aimed to reveal the medium-term impacts of the COVID-19 epidemic on case volumes and quality of intensive care for critically ill non-COVID-19 patients., Methods: Administrative data were used to investigate the trends in case volumes of admissions to intensive care units (ICUs) compared with the previous years. Standardized mortality ratios (SMRs) of non-COVID-19 ICU patients were calculated in each wave of the COVID-19 epidemic in Japan., Results: The ratios of new ICU admissions of non-COVID-19 patients to those in the corresponding months before the epidemic: 21% in May 2020, 8% in August 2020, 9% in February 2021, and 14% in May 2021, approximately concurrent with the peaks in COVID-19 infections. The decrease was greatest for new ICU admissions of non-COVID patients receiving invasive mechanical ventilation (IMV) on the first day of ICU admission: 26%, 15%, 19%, and 19% in the first, second, third, and fourth waves, respectively. No statistically significant change in SMR was observed in any wave of the epidemic; SMRs were 0.990 (95% uncertainty interval (UI), 0.962-1.019), 0.979 (95% UI, 0.953-1.006), 0.996 (95% UI, 0.980-1.013), and 0.989 (95% UI, 0.964-1.014), in the first, second, third, and fourth waves of the epidemic, respectively., Conclusions: Compared to the previous years, the number of non-COVID-19 ICU patients continuously decreased over the medium term during the COVID-19 epidemic. The decrease in case volumes was larger in non-COVID-19 ICU patients initially receiving IMV than those undergoing other initial treatments. The standardized in-hospital mortality of non-COVID-19 ICU patients did not change in any waves of the epidemic., Competing Interests: The authors declare that they have no competing interests.

Background: Pneumatosis intestinalis (PI) is a rare condition characterized by gas collection in the intestinal wall. We aimed to determine the etiology and affected segments associated with complications, treatment, and outcome., Methods: We conducted a multicenter epidemiological survey using a standardized data collection sheet in Japan. Complicating PI was defined as strangulation or bowel necrosis, bowel obstruction, adynamic ileus, sepsis, shock, and massive gastrointestinal bleeding requiring blood transfusion., Results: We enrolled 167 patients from 48 facilities. Multivariate analysis revealed that older age (adjusted OR, 1.05 and 95% confidence intervals [CI], 1.02-1.09, P = 0.0053) and chronic kidney disease (adjusted OR, 13.19 and 95% CI 1.04-167.62, P = 0.0468) were independent predictors of the small-bowel-involved type. Complicating PI was associated with the small-bowel-involved combined type (adjusted OR, 27.02 and 95% CI 4.80-152.01, P = 0.0002), the small-bowel-only type (adjusted OR, 3.94 and 95% CI 1.02-15.27, P = 0.0472), and symptomatic PI (adjusted OR, 16.24 and 95% CI 1.82-145.24, P = 0.0126). Oxygen therapy was performed in patients with a past history of bowel obstruction (adjusted OR, 13.77 and 95% CI 1.31-144.56, P = 0.0288) and surgery was performed in patients with complicating PI (adjusted OR, 8.93 and 95% CI 1.10-72.78, P = 0.0408). Antihypertensives (adjusted OR, 12.28 and 95% CI 1.07-140.79, P = 0.0439) and complicating PI (adjusted OR, 11.77 and 95% CI 1.053-131.526; P = 0.0453) were associated with exacerbation of PI. The complicating PI was the only indicator of death (adjusted OR, 14.40 and 95% CI 1.09-189.48, P = 0.0425)., Discussion: Small-bowel-involved type and symptomatic PI were associated with complications which were indicators of poor prognosis., (© 2022. The Author(s).)

Aim: The coronavirus disease 2019 (COVID-19) pandemic has left negative spillover effects on the entire health care system. Previous studies have suggested significant declines in cases of acute coronary syndrome (ACS) and primary percutaneous coronary intervention (PCI) during the COVID-19 pandemic., Methods: We performed a quasi-experimental, retrospective cohort study of ACS hospitalisations by using a multi-institutional administrative claims database in Japan. We used interrupted time series analyses to ascertain impacts on cases, treatment approaches, and in-hospital mortality before and after Japan's state of emergency to respond to COVID-19. The primary outcome was the change in ACS cases per week., Results: A total of 30,198 ACS cases (including 21,612 acute myocardial infarction and 8,586 unstable angina) were confirmed between 1 st July 2018 and 30 th June 2020. After the state of emergency, an immediate decrease was observed in ACS cases per week (-18.3%; 95% confidence interval, -13.1 to -23.5%). No significant differences were found in the severity of Killip classification (P=0.51) or cases of fibrinolytic therapy (P=0.74). The impact of the COVID-19 pandemic on in-hospital mortality in ACS patients was no longer observed after adjustment for clinical characteristics (adjusted odds ratio, 0.93; 95% confidence interval, 0.78 to 1.12; P=0.49)., Conclusions: We demonstrated the characteristics and trends of ACS cases in a Japanese population by applying interrupted time series analyses. Our findings provide significant insights into the association between COVID-19 and decreases in ACS hospitalisations during the pandemic.

Aims: The Coronavirus Disease 2019 (COVID-19) pandemic has had unprecedented effects on health care utilization for acute cardiovascular diseases. Although hospitalizations for acute coronary syndrome decreased during the COVID-19 pandemic, there is a paucity of data on the trends and management of heart failure (HF) cases. Furthermore, concerns have been raised that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase susceptibility to COVID-19. This study aimed to elucidate changes in HF hospitalizations from the COVID-19 state of emergency in Japan and investigated changes in the prescription of ACEIs and ARBs, and in-hospital mortality., Methods and Results: We performed an interrupted time series analysis of HF hospitalizations in Japan to verify the impacts of the COVID-19 state of emergency. Changes in the weekly volume of HF hospitalizations were taken as the primary outcome measure. Between 1 April 2018 and 4 July 2020, 109 429 HF cases required admission. After the state of emergency, an immediate decrease was observed in HF cases per week [-3.6%; 95% confidence interval (CI): -0.3% to -6.7%, P = 0.03]. There was no significant change in the prescription of ACEIs or ARBs after the state of emergency (4.2%; 95% CI: -0.3% to 8.9%, P = 0.07). The COVID-19 pandemic had no effect on in-hospital mortality among HF patients (5.3%; 95% CI: -4.9% to 16.6%, P = 0.32)., Conclusions: We demonstrated a decline in HF hospitalizations during the COVID-19 pandemic in Japan, with no clear evidence of a negative effect on the prescription of ACEIs and ARBs or in-hospital mortality., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The pandemic of the coronavirus disease 2019 (COVID-19) has affected health care systems globally. The aim of our study is to assess the impact of the COVID-19 pandemic on the number of hospital admissions for ischemic stroke by severity in Japan., Methods: We analysed administrative (Diagnosis Procedure Combination-DPC) data for cases of inpatients aged 18 years and older who were diagnosed with ischemic stroke and admitted during the period April 1 2018 to June 27 2020. Levels of change of the weekly number of inpatient cases with ischemic stroke diagnosis after the declaration of state of emergency were assessed using interrupted time-series (ITS) analysis. The numbers of patients with various characteristics and treatment approaches were compared. We also performed an ITS analysis for each group ("independent" or "dependent") divided based on components of activities of daily living (ADL) and level of consciousness at hospital admission., Results: A total of 170,294 cases in 567 hospitals were included. The ITS analysis showed a significant decrease in the weekly number of ischemic stroke cases hospitalized (estimated decrease: -156 cases; 95% confidence interval (CI): -209 to -104), which corresponds to -10.4% (95% CI: -13.6 to -7.1). The proportion of decline in the independent group (-21.3%; 95% CI: -26.0 to -16.2) was larger than that in the dependent group (-8.6%; 95% CI: -11.7 to -5.4)., Conclusions: Our results show a marked reduction in hospital admissions due to ischemic stroke after the declaration of the state of emergency for the COVID-19 pandemic. The independent cases were affected more in proportion than dependent cases., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The coronavirus disease (COVID-19) pandemic has caused unprecedented challenges for the medical staff worldwide, especially for those in hospitals where COVID-19-positive patients are hospitalized. The announcement of COVID-19 hospital restrictions by the Japanese government has led to several limitations in hospital care, including an increased use of physical restraints, which could affect the care of elderly dementia patients. However, few studies have empirically validated the impact of physical restraint use during the COVID-19 pandemic. We aimed to evaluate the impact of regulatory changes, consequent to the pandemic, on physical restraint use among elderly dementia patients in acute care hospitals., Methods: In this retrospective study, we extracted the data of elderly patients (aged > 64 years) who received dementia care in acute care hospitals between January 6, 2019, and July 4, 2020. We divided patients into two groups depending on whether they were admitted to hospitals that received COVID-19-positive patients. We calculated descriptive statistics to compare the trend in 2-week intervals and conducted an interrupted time-series analysis to validate the changes in the use of physical restraint., Results: In hospitals that received COVID-19-positive patients, the number of patients who were physically restrained per 1,000 hospital admissions increased after the government's announcement, with a maximum incidence of 501.4 per 1,000 hospital admissions between the 73rd and 74th week after the announcement. Additionally, a significant increase in the use of physical restraints for elderly dementia patients was noted (p = 0.004) in hospitals that received COVID-19-positive patients. Elderly dementia patients who required personal care experienced a significant increase in the use of physical restraints during the COVID-19 pandemic., Conclusion: Understanding the causes and mechanisms underlying an increased use of physical restraints for dementia patients can help design more effective care protocols for similar future situations., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The coronavirus disease (COVID-19) pandemic has caused unprecedented challenges for surgical staffs to minimize exposure to COVID-19 or save medical resources without harmful patient outcomes, in accordance with the statement of each surgical society. No research has empirically validated declines in surgical volume in Japan, based on the usage of surgical triage. We aimed to identify whether the announcement of surgical priorities by each Japanese surgical society may have affected the surgical volume decline during the 1st wave of this pandemic., Methods: We extracted 490,719 available cases of patients aged > 15 years who underwent elective major surgeries between July 1, 2018, and June 30, 2020. After the categorization of surgical specialities, we calculated descriptive statistics to compare the year-over-year trend and conducted an interrupted time series analysis to validate the decline of each surgical procedure., Results: Monthly surgical cases of eight surgical specialities, especially ophthalmology and ear/nose/throat surgeries, decreased from April 2020 and reached a minimum in May 2020. An interrupted time series analysis showed no significant trends in oncological and critical surgeries., Conclusion: Non-critical surgeries showed obvious and statistically significant declines in case volume during the 1st wave of the COVID-19 pandemic according to the statement of each surgical society in Japan., (© 2021. Springer Nature Singapore Pte Ltd.)

Many countries have implemented school closures as part of social distancing measures intended to control the spread of coronavirus disease 2019 (COVID-19). The aim of this study was to assess the early impact of nationwide school closure (March-May 2020) and social distancing for COVID-19 on the number of inpatients with major childhood infectious diseases in Japan. Using data from the Diagnosis Procedure Combination system in Japan, we identified patients aged 15 years or younger with admissions for a diagnosis of upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), influenza, gastrointestinal infection (GII), appendicitis, urinary tract infection (UTI), or skin and soft tissue infection (SSTI) between July 2018 and June 2020. Changes in the trend of the weekly number of inpatients between the two periods were assessed using interrupted time-series analysis. A total of 75,053 patients in 210 hospitals were included. The overall weekly number of inpatients was decreased by 52.5%, 77.4%, and by 83.4% in the last week of March, April, and May 2020, respectively, when compared on a year-on-year basis. The estimated impact was a reduction of 581 (standard error 42.9) inpatients per week in the post-school-closure period (p < 0.001). The main part of the reduction was for pre-school children. Remarkable decreases in the number of inpatients with URI, LRTI, and GII were observed, while there were relatively mild changes in the other groups.Conclusion: We confirmed a marked reduction in the number of inpatients with childhood non-COVID-19 acute infections in the post-school-closure period. What is Known: • Most countries have implemented social distancing measures to limit the spread of the novel coronavirus disease 2019 (COVID-19). • A large decrease in pediatric emergency visits has been reported from several countries after the social distancing. What is New: • Based on administrative claims data, a marked reduction in the number of inpatients for childhood non-COVID-19 acute infections was found in the post-school-closure period in Japan. • The magnitude of the reduction was different between the disease groups., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: The aim of this study was to examine the effects of evolocumab on favorable limb events in patients with chronic limb-threatening ischemia (CLTI)., Methods: A single-center, prospective observational study was performed on 30 patients with CLTI. The subjects were divided into 2 groups based on evolocumab administration: evolocumab-treated (E) group ( n=14) and evolocumab non-treated (non-E) group (n=16). The primary outcome was 12-month freedom from major amputation. The secondary outcomes were 12-month amputation-free survival (AFS), overall survival (OS), and wound-free limb salvage. The mean follow-up period was 18±11 months., Results: No significant difference was detected between the two groups for the 12-month freedom from major amputation (log-rank p=0.15), while the 12-month AFS rate was significantly higher in the E group than that in the non-E group (log-rank p=0.02). The 12-month OS rate in the E group was shown a tendency for improvement, as compared with that in the non-E group (log-rank p=0.056). Evolocumab administration was not associated with a significant change in freedom from major amputation (HR, 0.23, 95% CI, 0.03-2.07, p=0.19). However, evolocumab administration was related to a tendency for improvement of AFS and OS (HR, 0.13, 95% CI, 0.02-1.06, p=0.056; HR, 0.16, 95% CI, 0.02-1.37, p=0.09, respectively). Moreover, The E group had a higher proportion of wound-free limb salvage at 12 months (92% vs. 42%, p=0.03)., Conclusion: Evolocumab administration was associated with a better AFS outcome in patients with CLTI. Long-term administration of evolocumab over 12 months contributed to improving proportion of wound-free limb salvage.

Background: Addressing cachexia in chronic heart failure (CHF) patients is an urgent issue in Japan, the most aged country in the world. We investigated the possible relationships between cachexia and, metalloproteinases and haemodynamics assessed by the cardiac catheterization. We also clarified the prognostic value of cardiac cachexia in the Japanese CHF population., Methods and Results: A total of 370 participants (median age, 69 years; 35% women) were included. The haemodynamic effects of cachexia were analysed by right heart catheterization. The serum levels of matrix metalloproteinase (MMP) and tissue inhibitors of MMP (TIMP), as myocardial collagen turnover markers, were also assessed. Cachexia was present in 88 patients (31%). Overall, 59 patients (16%) had all-cause death. Serum MMP-2 and TIMP-2 levels were higher in cachectic patients than in noncachectic patients (797.5 [649.0-1066.8] vs 610.0 [461.8-756.8] ng/mL; P = .004 and 39.0 [28.0-49.0] vs 24.0 [19.0-37.0] ng/mL; P = .008, respectively). Cachectic patients had greater values of pulmonary vascular resistance (PVR) (161.9 [119.4-225.4] vs 127.8 [90.7-164.8] dynes/sec/cm -5 , P = .020). Kaplan-Meier survival analysis demonstrated higher probabilities of all-cause death in the cachexia group (log-rank P = .010). Cox proportional hazards modelling showed cachexia was an independent predictor of mortality (hazard ratio, 1.89; 95% confidence interval, 1.06-3.37; P = .029). The random forest model showed that C-reactive protein, age, haemoglobin, PVR and MMP-2 were predictors of cardiac cachexia., Conclusions: Cachexia, applying the globally accepted definition, was associated with adverse outcomes in the Japanese CHF population and accompanied by increased activity of MMP species and PVR., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: The management of severe adverse events (AEs) is important in safely and effectively providing chemotherapy to older adults with diffuse large B-cell lymphoma (DLBCL). However, reports on simple and DLBCL-specific predictive models for treatment-related toxicity in elderly individuals are scarce. The aim of this study was to examine the usefulness of Geriatric 8 (G8) in predicting treatment-related severe AEs, nonhematological toxicity, and febrile neutropenia in older adults with DLBCL in real-world practice., Materials and Methods: We conducted a multicenter, retrospective study on 398 consecutive patients with DLBCL (aged ≥65 years) who received standard therapy at three centers in Japan (University of Fukui Hospital, the Fukui Prefectural Hospital, and the Japanese Red Cross Fukui Hospital), between 2007 and 2017., Result: Multivariate logistic analysis demonstrated that the G8 score was an independent predictive factor for severe AEs. Moreover, a logistic regression model with restricted cubic spline showed a nonlinear association between the incidence of severe AEs and the G8 score. According to receiver operating characteristic analysis, the most discriminative cutoff value of the G8 for the incidence of severe AEs was 11, with an area under the curve value of 0.670. AEs occurred most often in the first course of chemotherapy and decreased as the course progressed., Conclusion: The G8 score, an easy-to-use geriatric assessment tool, can be a useful prediction model of treatment-related severe AEs during standard therapy in older adults with DLBCL., Implications for Practice: In older patients with diffuse large B-cell lymphoma (DLBCL), to accurately predict the risk of severe adverse events (AEs) in advance is essential for safe and effective treatment. This study demonstrated that the Geriatric 8 score, a simple and established geriatric assessment tool, indicated a high predictive ability for occurrence of therapy-related severe AEs in elderly patients with DLBCL who were treated with standard treatment., (© 2020 AlphaMed Press.)

Age-related changes in muscle strength and physical functions, and the association between vitamin D status and skeletal muscle functions were investigated in 36 men (21-90 years old) and 52 women (21-104 years old). Significant ageing-related decreases in several skeletal muscle functions and serum 25-hydroxyvitamin D [25(OH)D] levels were observed in both men and women. Cut-off values for the Timed up and go (TUG) test, walking speed, handgrip strength and Barthel Index (BI) detecting walking difficulties in the receiver operating characteristic (ROC) analysis were 11.1 sec, 0.60 m / sec, 17.0 kg, and 90.0 in males, and 28.6 sec, 0.43 m / sec, 13.9 kg, and 67.5 in females, respectively. By comparing personal present data of muscle strength with these cut-off values, people can easily understand their process to walking difficulty. Therefore, these results are important and useful to avoid or to delay a handicapped and dependent status by improving the vitamin D level, rehabilitation and nursing care. J. Med. Invest. 68 : 48-52, February, 2021.

An intervention study was conducted to investigate the effects of daily 1,000-IU vitamin D-fortified milk intake on skeletal muscle mass, power, physical function and nutrition status in 26 healthy people and 8 older adults living in a nursing home. The serum 25-hydroxyvitamin D [25(OH)D] level was 13.4 ± 0.8 ng / mL and it markedly increased to 29.6 ± 0.9 ng / mL after daily 1000-IU vitamin D-fortified milk intake for 6 months. Handgrip strength (kg) also significantly increased in the 21-50 years and total groups, and male subjects, and the timed up and go test significantly improved in the 21-50 years and total groups, and female subjects after 6-month vitamin D intake. However, there were no significant differences between baseline and post-treatment in the Barthel Index (BI), walking speed (m / sec) or skeletal muscle mass (kg, % of BW, kg / m2). Therefore, the present study suggested that vitamin D-fortified milk intake is effective at improving muscle strength and physical function in Japanese, although further studies are needed, particularly for older adults. J. Med. Invest. 68 : 249-255, August, 2021.

Background: In response to the coronavirus diseases 2019 (COVID-19) pandemic, the Japanese government declared a state of emergency on April 7, 2020. Six days earlier, the Japan Surgical Society had recommended postponing elective surgical procedures. Along with the growing public fear of COVID-19, hospital visits in Japan decreased., Methods: Using claims data from the Quality Indicator/Improvement Project (QIP) database, this study aimed to clarify the impact of the first wave of the pandemic, considered to be from March to May 2020, on case volume and claimed hospital charges in acute care hospitals during this period. To make year-over-year comparisons, we considered cases from July 2018 to June 2020., Results: A total of 2,739,878 inpatient and 53,479,658 outpatient cases from 195 hospitals were included. In the year-over-year comparisons, total claimed hospital charges decreased in April, May, June 2020 by 7%, 14%, and 5%, respectively, compared to the same months in 2019. Our results also showed that per-case hospital charges increased during this period, possibly to compensate for the reduced case volumes. Regression results indicated that the hospital charges in April and May 2020 decreased by 6.3% for hospitals without COVID-19 patients. For hospitals with COVID-19 patients, there was an additional decrease in proportion with the length of hospital stay of COVID-19 patients including suspected cases. The mean additional decrease per COVID-19 patient was estimated to 5.5 million JPY., Conclusion: It is suggested that the hospitals treating COVID-19 patients were negatively incentivized., Competing Interests: The authors have declared that no competing interests exist.

Aims: The sequential organ failure assessment (SOFA) score has been a widely used predictor of outcomes in the intensive care unit, whereas short-term and long-term survivals of heart failure (HF) patients are predicted by the American Heart Association Get With the Guidelines-Heart Failure (GWTG-HF) risk score. The purpose of present study was to examine whether the SOFA score on admission is more useful for predicting long-term mortality in acute HF patients than the GWTG-HF risk score., Methods and Results: A total of 269 patients (mean age, 78.5 ± 10.9 years; all-cause mortality, 53.9%) seen in a single facility from January 2007 to December 2016 were enrolled retrospectively. They were followed up for a mean of 32.1 ± 22.3 months. All-cause death was associated with higher SOFA and GWTG-HF risk scores. However, no significant difference was observed in the area under the curve value between the scores. Kaplan-Meier survival analysis indicated that higher SOFA scores (P < 0.001) and GWTG-HF risk scores (P < 0.001) were related to increased probabilities of all-cause death. On multivariate Cox proportional hazard model analysis, the SOFA score (P < 0.001) and GWTG-HF (P < 0.001) score were independent predictors of all-cause death. Incorporating the SOFA score into the GWTG-HF risk score yielded a significant net reclassification improvement and integrated discrimination improvement. On decision curve analysis, the net benefit of the SOFA score model when compared with the reference model was greater across the range of threshold probabilities., Conclusions: In acute HF patients, long-term all-cause mortality can be predicted by the SOFA score. Discriminative performance metrics, such as net reclassification improvement, integrated discrimination improvement, and decision curve analysis, for predicting mortality were improved when the SOFA score was incorporated., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: The oral vasopressin-2 receptor antagonist, tolvaptan, causes aquaresis and improves symptoms in patients with congestive heart failure. However, few studies have explored the effect of tolvaptan in acute heart failure (AHF) patients ≥90 years old., Methods: This study enrolled 106 AHF patients treated with tolvaptan added to standard therapy. The subjects were divided into 2 groups: ≥90-year-old patients (over-90 group, mean 92 ± 2 years, n = 45) and <90-year-old patients (under-90 group, mean 76 ± 11 years, n = 61). Patients' characteristics were assessed, and efficacy and safety were compared between the 2 groups., Results: The over-90 group had a lower proportion of male patients, lower body weight, and higher ejection fraction. The under-90 group had significantly higher prevalence of ischemic heart disease and diabetes mellitus. There were no significant differences between the 2 groups in total urine volume at 24 and 48 hours (1934 ± 983 mL vs 1816 ± 1028 mL, P = 0.58 and 3806 ± 1444 mL vs 4078 ± 1851 mL, P =0.47, respectively), the mean change in body weight (-3.0 ± 2.7 kg vs -2.6 ± 2.6 kg, P = 0.50), improvement of congestive symptoms, changes in serum sodium and creatinine levels, the incidences of hypernatremia (n = 0, 0% vs n = 1, 1.6%, P = 0.63), and worsening renal function (n = 9, 20% vs n = 17, 28%, P = 0.48)., Conclusion: The efficacy and safety of tolvaptan in AHF patients aged more than 90 years were comparable to those of <90 years old. Tolvaptan provides a complementary therapeutic option for AHF patients aged more than 90 years.

Suprascapular nerve entrapment is rarely treated by neurosurgeons in Japan. However, it is often observed in post-stroke patients and in cases of accessory nerve injury as a complication of posterior fossa craniotomy. We report a case of suprascapular nerve entrapment due to superior transverse scapular ligament, which was successfully diagnosed and surgically treated. The patient was a 66-year-old female who used be a janitor. She complained of dysesthesia around the shoulder. The diagnosis was made based on the characteristic neurological findings including pain around the scapula, supraspinatus muscle weakness, and favorable but temporary response to suprascapular nerve block. After undergoing conservative management for one and a half year, she decided to undergo the nerve decompression surgery. The surgical treatment was performed under microscope with neuromonitoring. Following surgery, the painful area was dramatically reduced. We believe that suprascapular nerve disorders can be treated with careful neurological evaluation by neurosurgeons.

To discriminate the trace-rutinosidase variety of Tartary buckwheat 'Manten-Kirari', we developed DNA markers based on RNA polymorphism. Specifically, we mapped 17.76 GB RNA sequences, obtained using HiSeq2000, to create 11,358 large contigs constructed de novo from 'Manten-Kirari' RNA derived from GS-FLX+ titanium. From these, we developed eight DNA markers corresponding to single- to four-nucleotide polymorphisms between 'Manten-Kirari' and 'Hokkai T8', which is representative of normal rutinosidase content varieties in Japan. Using these markers, 'Manten-Kirari' was discriminated from 'Hokkai T8' by eight markers, from major Tartary buckwheat varieties by three markers, and from common buckwheats by two markers. We also performed direct PCR from flour and dried noodle made with 'Manten-Kirari' and 'Hokkai T8'. Based on the results, the DNA markers developed are promising for discriminating 'Manten-Kirari'. This is the first study to develop a DNA marker to discriminate varieties in the Polygonaceae family including buckwheat species., (Copyright © 2019. Published by Elsevier Ltd.)

Background: The utility of pressure waveform analyses to assess pulmonary vein (PV) occlusions has been reported in cryoballoon PV isolation (CB-PVI) using first-generation CBs. This prospective randomized study compared the procedural and clinical outcomes of pressure-guided and conventional CB-PVI., Methods and Results: Sixty patients with paroxysmal atrial fibrillation underwent CB-PVI with 28-mm second-generation CBs. PV occlusions were assessed either by real-time pressure waveforms without contrast utilization (pressure-guided group) or contrast injections (conventional group) and randomly assigned. Before the randomization, 24 patients underwent pressure-guided CB-PVIs. In the derivation study, a vein occlusion was obtained in 88/96 (91.7%) PVs among which 86 (97.7%) were successfully isolated by the application. In the validation study, the nadir balloon temperature and total freezing time did not significantly differ per PV between the two groups. The positive predictive value of the vein occlusion for predicting successful acute isolations was similar (93 of 103 [90.2%] and 89 of 98 [90.8%] PVs; P = 1.000), but the negative predictive value was significantly higher in pressure-guided than angiographical occlusions (14 of 17 [82.3%] vs 7 of 22 [31.8%]; P = .003). Both the procedure (57.7 ± 14.2 vs 62.6 ± 15.8 minutes; P = .526) and fluoroscopic times (16.3 ± 6.4 vs 20.1 ± 6.1; P = .732) were similar between the two groups, however, the fluoroscopy dose (130.6 ± 97.7 vs 353.2 ± 231.4 mGy; P < .001) and contrast volume used (0 vs 17.5 ± 7.7 mL; P < .001) were significantly smaller in the pressure-guided than conventional group. During 27.8 (5-39) months of follow-up, the single procedure arrhythmia freedom was similar between the two groups (P = .438)., Conclusions: Pressure-guided second-generation CB-PVIs were similarly effective and as safe as conventional CB-PVIs. This technique required no contrast utilization and significantly reduced radiation exposure more than conventional CB-PVIs., (© 2019 Wiley Periodicals, Inc.)

Cavo-tricuspid isthmus (CTI) anatomies are highly variable, and specific anatomies lead to a difficult CTI ablation. This study aimed to compare the clinical utility of angiography and intracardiac echocardiography (ICE) in evaluating CTI anatomies, and to investigate the impact of the CTI anatomy on the procedure when the ablation tactic was adjusted to the anatomy. This study included 92 consecutive patients who underwent a CTI ablation. The CTI morphology was assessed with both right atrial angiography and ICE before the ablation, and the ablation tactic was adjusted to the anatomy. The mean CTI length was 34 ± 9 mm. On ICE imaging, 21 (23%) patients had a flat CTI, while 41 (45%) had a concave CTI with a mean depth of 5.6 ± 2.7 mm. The remaining 30 (32%) had a distinct pouch with a mean depth of 6.4 ± 2.3 mm, located at the posterior, middle, and anterior isthmus in 15, 14, and 1 patients, respectively. The Eustachian ridge (ER) was visualized in 46 (50%) patients. On angiography, a pouch and ER were detected in 22 and 15 patients, but not in the remaining 8 and 31, respectively. A complete CTI block line was created in all patients without any complications. The CTI anatomy did not significantly impact any procedural parameters. ICE was superior to angiography in evaluating the detailed CTI anatomy, especially pouches and the ER. An adjustment of the ablation tactic to the anatomy could overcome the procedural difficulties of the CTI ablation in cases with specific anatomies.

A prospective, multicenter, phase II study was performed to assess the efficacy and safety of thalidomide maintenance therapy at different doses in Japanese multiple myeloma (MM) patients. This study included 34 patients (median age, 74 years) who were previously treated with not more than three prior therapies and whose response status was evaluated as at least stable disease. They were randomized into Group A (no maintenance; 12 patients), Group B (50 mg thalidomide maintenance; 12 patients), and Group C (100 mg thalidomide maintenance; 10 patients), respectively. Thalidomide maintenance therapy resulted in improved depth of response in three cases (13.6%) and sustained response after induction therapy in eight cases (36.4%). Two-year progression-free survival (PFS) was 25.0%, 33.3%, and 77.8% in Groups A, B, and C, respectively, and was significantly higher in Group C than in Group A (p = 0.005). There was no difference in the incidence of hematological or non-hematological adverse events between Groups B and C. The current study demonstrates that maintenance with daily thalidomide at 100 mg, but not 50 mg, improved depth of response and prolonged PFS, and that this treatment was feasible for use in Japanese MM patients.

Background: Capsule endoscopy can be used to identify the early stage of small bowel Crohn's disease (CD). We evaluated significant small bowel capsule endoscopy (SBCE) findings that can lead to early diagnosis of CD., Methods: We retrospectively accumulated clinical and SBCE data of 108 patients (63 with and 45 without CD). Types of small bowel mucosal injuries, including erosion, ulceration, and cobblestone appearance, and the alignment of diminutive lesions were compared between patients with and without CD. Inter- and intra-observer agreement in the determination of lesions was assessed in 25 pairs of SBCE from the two groups., Results: Under SBCE, cobblestone appearance (33% vs. 2%, p < 0.0001), longitudinal ulcers (78% vs. 20%, p < 0.0001), and irregular ulcers (84% vs. 60%, p < 0.01) were more frequently found in patients with CD. Linear erosion (90% vs. 38%, p < 0.0001) and irregular erosion (89% vs. 64%, p < 0.005) were also more frequent in patients with CD. Furthermore, circumferential (75% vs. 9%, p < 0.0001) and longitudinal (56% vs. 7%, p < 0.0001) alignment of diminutive lesions, mainly observed in the 1st tertile of the small bowel, was more frequent in patients with CD. Good intra-observer agreement was found for ulcers, cobblestone appearance, and lesion alignment. However, inter-observer agreement of SBCE findings differed among observers., Conclusions: Circumferential or longitudinal alignment of diminutive lesions, especially in the upper small bowel, may be a diagnostic clue for CD under SBCE, while inter-observer variations should be cautiously considered when using SBCE.

The aim of this study was to evaluate the relationships among the traditional risk factors, lipid profile, and pentraxin-3 in stable angina (SAP). Plasma pentraxin-3 and serum LDL, HDL, and high-sensitivity CRP levels were measured in 163 SAP and 28 non-coronary artery disease (CAD) patients. Their relationships with five risk factors, hypertension (HT), dyslipidemia (DL), diabetes mellitus (DM), obesity (body mass index: BMI > 25 kg/m 2 ), and high age (> 75 years), were evaluated. No significant difference was observed in the pentraxin-3 level between patients in SAP and in non-CAD [2.1 (1.4-3.5) ng/ml versus off 2.6 (1.6-3.8) ng/ml, P = 0.56). In SAP patients, pentraxin-3 levels decreased with more risk factors, according to the number of 3 traditional risk factors (HT, DL, and DM) and the number of 5 expanded risk factors (HT, DL, DM, obesity, and high age) (P for trend = 0.01 and 0.05, respectively). Pentraxin-3 showed a positive association with HDL (rs = 0.229; P = 0.050) and an inverse association with LDL (rs = - 0.224; P = 0.045). On multiple logistic regression, the number of 3 traditional risk factors was a significant predictor of pentraxin-3 levels (odds ratio = 0.444; 95% confidence interval  0.205-0.963, P = 0.040) in SAP patients. In SAP patients, the cardiovascular risk factor burden remained a negative impact on pentraxin-3 levels after multivariate analysis, suggesting that they have distinct roles in atherosclerosis.Trial registration: UMIN000023837.

Objective: To understand the actual condition of orthodontic treatment in team care for patients with syndromic craniosynostosis (SCS) in Japan., Design: A nationwide collaborative survey., Setting: Twenty-four orthodontic clinics in Japan., Patients: A total of 246 patients with SCS., Main Outcome Measure: Treatment history was examined based on orthodontic records using common survey sheets., Results: Most patients first visited the orthodontic clinic in the deciduous or mixed dentition phase. Midface advancement was performed without visiting the orthodontic clinic in about a quarter of the patients, and more than a half of the patients underwent "surgery-first" midface advancement. First-phase orthodontic treatment was carried out in about a half of the patients, and maxillary expansion and protraction were performed. Tooth extraction was required in about two-thirds of patients, and the extraction of maxillary teeth was required in most patients. Tooth abnormalities were found in 37.8% of patients, and abnormalities of maxillary molars were frequently (58.3%) found in patients who had undergone midface surgery below the age of 6 years., Conclusions: Many patients underwent "surgery-first" midface advancement, and visiting the orthodontic clinic at least before advancement was considered desirable. First-phase orthodontic treatment should be performed considering the burden of care. Midface advancement below the age of 6 years had a high risk of injury to the maxillary molars. This survey is considered useful for improving orthodontic treatment in team care of patients with SCS.

The object of this study was to determine the efficacy and safety of brain hypothermia therapy (BHT) for neonates with severe birth asphyxia in our neonatal intensive care unit (NICU). We retrospectively reviewed medical records to analyze the prognosis and the factors affecting the prognosis of 21 patients who underwent BHT at the NICU between 2001 and 2007. The prognosis of those 21 patients at the time of discharge from the NICU was as follows: good-11 patients (52.4%); disability-5 patients (23.8%); and death-5 patients (23.8%). The ten poor prognosis patients (disability: 5, death: 5) had a shorter gestational period, a lower Apgar score, and a significantly higher blood lactate level in comparison with good-prognosis newborns. In particular, a gestational period of less than 34 weeks (3 patients) and a blood lactate level of at least 200 mg/dl (6 out of 7 patients) are considered to be factors for a poor prognosis. In addition, intraventricular hemorrhage was recorded in 7 patients of the 10 poor-prognosis patients and 4 of those patients developed acute renal failure during BHT. Consequently, these disorders are considered to worsen the prognosis. This study supports the efficacy and safety of BHT for neonates with severe birth asphyxia. On the other hand, BHT for the above mentioned types of high-risk patients still requires further consideration for the adoption and methods of BHT.

Teleosts comprise more than half of all vertebrate species and have adapted to a variety of marine and freshwater habitats. Their genome evolution and diversification are important subjects for the understanding of vertebrate evolution. Although draft genome sequences of two pufferfishes have been published, analysis of more fish genomes is desirable. Here we report a high-quality draft genome sequence of a small egg-laying freshwater teleost, medaka (Oryzias latipes). Medaka is native to East Asia and an excellent model system for a wide range of biology, including ecotoxicology, carcinogenesis, sex determination and developmental genetics. In the assembled medaka genome (700 megabases), which is less than half of the zebrafish genome, we predicted 20,141 genes, including approximately 2,900 new genes, using 5'-end serial analysis of gene expression tag information. We found single nucleotide polymorphisms (SNPs) at an average rate of 3.42% between the two inbred strains derived from two regional populations; this is the highest SNP rate seen in any vertebrate species. Analyses based on the dense SNP information show a strict genetic separation of 4 million years (Myr) between the two populations, and suggest that differential selective pressures acted on specific gene categories. Four-way comparisons with the human, pufferfish (Tetraodon), zebrafish and medaka genomes revealed that eight major interchromosomal rearrangements took place in a remarkably short period of approximately 50 Myr after the whole-genome duplication event in the teleost ancestor and afterwards, intriguingly, the medaka genome preserved its ancestral karyotype for more than 300 Myr.

We evaluated the clinical course of acute myeloid leukemia (AML) and the levels of WT1 mRNA in 191 AML patients. Of 114 previously untreated patients with AML, 107 cases were positive for WT1 mRNA (93.9% : 107/114). WT1 mRNA expression-levels declined to below 50 copies/microg RNA ("negative") after remission was achieved in all 66 patients who achieved remission and 84.8% (47/54) cases were "negative" at the end of the follow-up periods. On the other hand, WT1 mRNA was expressed in 87.0% of non-remission cases (47/54), maintaining 50 copies/microg of RNA or higher ("positive"). In all 29 cases who relapsed during the follow-up observation period after achieving remission, WT1 mRNA levels declined transiently approximately around the time of achieving remission and then rose again when the disease relapsed. Moreover, we determined the time of elevation of WT1 mRNA in 29 relapsed cases. In 79.3% of relapsed cases (23/29), WT1 mRNA levels rose above 200 copies/microg RNA, 43 days (median) before the diagnosis of "relapse". Given the percent of the correct diagnosis, WT1 mRNA at 200 copies/microg RNA appeared to be a reasonable cut-off level for early detection of AML-relapse. The WT1 mRNA level reflected the clinical condition. Taken together, these findings indicate that WT1 mRNA levels allow us to detect the presence of so-called "minimal residual disease" (leukemic cells) that cannot be detected by morphological examination. Besides these promising data, this kit is suitable for routine monitoring of AML because this kit utilizes peripheral blood as a test specimen, reducing the patient's burden at the time of collection of clinical samples as compared with bone marrow aspirate.

An influenza C virus was isolated from a Japanese traveler who had visited Malaysia in April 1999. Phylogenetic analysis indicated that the genome composition of this virus was distinct from that of any other strain isolated in Japan. The possibility that a genetically unique influenza C virus was introduced into Japan by a traveler is shown.

A reassortant influenza A H1N2 virus was isolated from a returning traveller arriving at Nagoya International Airport, Japan from Indonesia in May, 2002. A Hemagglutination inhibition test revealed that the virus was similar to a vaccine strain of A/NewCaledonia/20/99. A phylogenetic analysis demonstrated that the virus forms a cluster with other influenza A H1N2 viruses isolated in other countries. The reassortment event was theoretically assumed to have occurred between the 1999/2000 and 2000/2001 influenza seasons. Neither A H1N2 nor A H3N1 virus was detected from 256 isolates of AH1 or 177 of AH3 influenza viruses isolated in Aichi Prefecture, Japan between the 1999/2000 and 2001/2002 influenza seasons. This finding suggests the importance of influenza surveillance at an airport quarantine office to detect promptly a novel influenza virus penetrating to Japan.

Background: Soya foods, a staple in several Asian countries, have received increasing attention because of their nutritional properties and their high isoflavone content. We have shown recently abnormal pharmacokinetics of soya isoflavones following acute oral intake, in soya-naive end-stage renal disease (ESRD) patients. No information is available, however, about blood levels of soya isoflavones in ESRD patients with habitual soya intake. Additionally, no information is available about the conjugation profile of these compounds in ESRD patients., Methods: To assess the relationship between habitual soya intake on blood isoflavone levels in ESRD patients, we recorded dietary soya food intake and analysed circulating levels of soya isoflavones in randomly selected, clinically stable haemodialysis patients from the United States (n = 20), Thailand (n = 17) and Japan (n = 20). Dietary records and three weekly blood samples were collected from each participant. Combined isoflavones and individual genistein, daidzein, glycitein and O-desmethylangolensin (DMA) were analysed in serum by liquid chromatography/mass spectrometry. Lipid phase micronutrients, including tocopherols, carotenoids and retinol were also measured to compare ethnic differences in isoflavones with those of more common lipid soluble antioxidant micronutrients., Results: Soya intake was higher in Japanese than in Thai patients and it was negligible in the US patients. Blood levels of genistein were very elevated and significantly higher in the Japanese patients (1128 +/- 205 nM), as compared with the Thai and US patients (258 +/- 64 and 168 +/- 49 nM, respectively; P < 0.001). The other isoflavones followed the same trend. Daidzein was more concentrated than genistein in the dialysis patients. Robust correlation was present between weekly soya intake and blood isoflavone levels (r = 0.56, P < 0.001). Despite very high total isoflavone concentrations, the levels of unconjugated and sulphated isoflavones in the Japanese patients were comparable to those described in healthy subjects. Compared with the striking difference in isoflavones, more easily accessible dietary antioxidants, including tocopherols, carotenoids and retinol, differed only minimally or not at all in the three groups., Conclusions: ESRD patients appear to accumulate isoflavones as a function of dietary soya intake, resulting in blood concentrations that are higher than those reported in subjects with preserved kidney function. Even in the presence of very elevated total isoflavone levels, the concentrations of the unconjugated and sulphated fractions are comparable to those of healthy subjects. A discrepancy is noted between accumulation of soya isoflavones and other more common lipid-soluble antioxidant micronutrients.

Since the discovery of GB virus-C (GBV-C) and hepatitis G virus (HGV), many studies have been performed. These viruses are now known to be parenterally, as well as sexually transmitted. A phylogenetic analysis also revealed that GBV-C has five major genotypes: type 1 predominates in West Africa, type 2 in Europe and the United States, type 3 in parts of Asia, type 4 in Southeast Asia, and type 5 in South Africa. Despite the number of reports so far, there have been few large-scale surveys of homosexual men to determine the prevalence of the GBV-C/HGV infections. We examined the levels of GBV-C/HGV viremia in 297 homosexual men who attended the Nagoya Lesbian and Gay Revolution held in Nagoya, Japan. Reverse transcription-polymerase chain reaction (RT-PCR)/nested PCR of the GBV-C/HGV 5 ' -non-coding region (NCR), and base sequence analyses showed that the infection rate was 12.5%, and genotypes in this population were classified into type 2 (32%) and type 3 (68%). None were classified as types 1, 4, or 5 in this study. Our results indicate that the GBV-C/HGV type 2 seen mainly in Europe and the US is spreading widely in Japan, especially in the Nagoya district.

In order to conduct a survey of influenza viruses entering Japan via travellers arriving by airplanes, gargle solutions were collected from passengers who reported to the quarantine station of Nagoya International Airport complaining of respiratory symptoms. From 504 samples collected between August 1996 and March 1999, 30 influenza virus strains were isolated. Twenty-eight of the isolates were influenza A (H3N2) viruses and two were influenza B viruses. No H1N1 virus was isolated. Among 28 isolates of H3N2 virus, 3 strains were obtained outside the influenza season. Nucleotide sequences of the haemagglutinin (HA) genes of these isolates along with those from domestic patients were analysed in order to determine the influence of imported influenza viruses by travellers on epidemics in Japan. From the phylogenetic and chronological aspects, the possibility was suggested in one case in 1997/8 and two in the 1998/9 season that imported virus by travellers may have influenced the domestic influenza epidemics.

Orientia tsutsugamushi was isolated from one of 8 patients' sera in Aichi Prefecture, and was identified to have the same antigenicity with the KN-2 strain (KN-2 like) based on the reactivity with 13 types of strain-specific or cross-reactive monoclonal antibodies to Karp, Gilliam, and Kato strains. Four isolates from 4 unfed larvae and adult of Leptotrombidium pallidum were also classified as the KN-3 like strains. Using indirect immunofluorescence, sera from 20 patients with tsutsugamushi disease were tested for reactivity with KN-1, KN-2, KN-3, and GJ-1 strains, isolated from patients in Gifu Prefecture. Fifteen sera showed the highest titer against KN-2 strain in Immunogloburin M (IgM). Of the other 5, three were higher for KN-3 strain in IgM, and two were KN-1 or GJ-1, respectively. These results suggested that KN-2 like strains were prevalent in the region where the number of patients has been ranked the highest in Aichi Prefecture. KN-1, KN-3, and GJ-1 like strains were also existed in this area. KN-3 like strain was likely to be distributed in another area. Aichi Prefecture.

Two phenotypes of human influenza A(H1N1) virus are currently circulating in Japan. One (group 1) agglutinates both chicken and goose red blood cells (CRBC and GRBC), the other (group 2) agglutinates GRBC but not CRBC. In the 1995/6 season, group 2 viruses accounted for 70% of the H1N1 viruses isolated in MDCK cells. The 1995/6 viruses were located on two branches of the genetic tree. One branch contained both group 1 and group 2 viruses and the other branch contained only group 2 viruses. Group 2 viruses had aspartic acid at residue 225 in the haemagglutinin (HA) protein, the key amino acid residue for group 2 phenotype. The HA protein of group 1 viruses had a change from aspartic acid to asparagine at residue 225 and the expressed HA protein of these viruses adsorbed CRBC. Serial passage of group 2 viruses in MDCK cells or embryonated chicken eggs caused these viruses to gain the ability to agglutinate CRBC. MDCK-adapted viruses had the same amino acid sequences of HA polypeptide as the original ones, but egg-adapted viruses had changed amino acid sequences. The expressed HA protein from one egg-adapted virus that originally belonged to group 2 adsorbed CRBC.

In 1990, we conducted a questionnaire survey showing that many nurses had incorrect knowledge of AIDS resulting in inappropriate attitudes toward AIDS patients. Following the first survey conducted in 1990, nurses were given various forms of AIDS education. The effectiveness of the AIDS education requires assessment. Therefore a second questionnaire survey was performed in 1993 to assess changes in nurses' knowledge and attitudes regarding AIDS. The same questionnaire as used in the first survey was sent to a random sample of nurses working at general hospitals in Mie Prefecture, Japan. The questionnaire covered knowledge of AIDS, psychological responses, attitudes and conduct around infected persons and measures against AIDS. Results of both questionnaire surveys showed that the majority of nurses acquired their knowledge predominantly from the mass media, and a large number of nurses worried that AIDS would spread in Japan. Almost half of the nurses were worried that they might be infected with AIDS. The second survey showed that nurses who acquired knowledge of AIDS from printed material, pamphlets and other educational resources, including lectures had increased. In 1993, many more nurses had accurate knowledge compared to the number in the first survey. In 1993 the number of nurses who discriminated against AIDS patients and HIV-infected persons had decreased.

Virological examinations were performed on stools obtained from 1,264 overseas travellers with diarrhea at Nagoya International Airport between 1986 and 1991. Group A rotavirus was detected in 11 samples (0.87%) by latex agglutination method, but other viral agents such as atypical rotaviruses and small round structured viruses were not observed by electron microscopic analysis. Rotaviruses were detected in various age groups, but the positive rate of rotavirus in females (6/398) was higher than that in males (5/866). Seasonal variation in the detection of rotavirus was observed. Entero 71 was isolated from one of 11 rotavirus-positive cases, but the other 10 cases were not associated with enteroviruses. All rotavirus-positive cases were negative for isolation of enteropathogenic bacteria.

Circumstantial evidence from electron microscopic and immunological studies support the view that Paget's disease of bone represents a slow virus infection. However, there is only limited information available regarding its electron microscopic, enzyme and immunocytochemical characteristics. Two cases were studied using electron microscopy with particular emphasis on the inclusions in osteoclasts. Detailed ultrastructural and cytochemical studies including immuno-electron microscopy were performed. Some osteoclasts demonstrated specific virus-like structures composed of aggregations of microtubules in the nucleus and cytoplasm. The structures were easily digested by trypsin or protease, and were sensitive to RNase, which provided substantial evidence of a proteinaceous nature and inclusion of ribonucleic acid. Immunocytochemical examination identified binding of anti-respiratory syncytial virus and anti-measles virus antibodies in the tissue obtained from one of the two cases examined. The presence of viral antigens in structures in the cytoplasm of Pagetic osteoclasts supports the theory of paramyxovirus involvement in this disease.

Levels of understanding and knowledge regarding AIDS were investigated for medical personnel working at general hospitals with more than 100 beds in Mie Prefecture by means of a questionnaire during May to June, 1990. The questionnaire covered general knowledge of AIDS, psychological response, attitudes and actions taken toward infected persons, and societal countermeasures against AIDS. Responses from 1,516 nurses and assistant nurses were statistically investigated among medicare persons. Mass media was the major source of knowledge on AIDS for the nurses and assistant nurses. Level of understanding on AIDS, however, appeared to be rather low, which may be due to difficulty in obtaining accurate information on AIDS and also due to lack of motivation to study. The responses of nurses were more positive than for assistant nurses for action taken in hypothetical cases of infection to themselves, spouses or familiar persons. Similar differences were also shown in responses regarding societal countermeasures against the disease.

In March 1989 a large outbreak of acute gastroenteritis occurred simultaneously among schoolchildren and teachers at nine elementary schools in Toyota City, Japan. Illness was observed in 3236 (41.5%) of 7801 schoolchildren and 117 (39.4%) of 297 teachers. The main clinical symptoms were diarrhoea, vomiting, nausea and abdominal pain. Gastroenteritis was significantly associated with the consumption of school lunch served by one particular lunch preparation centre. One food handler at the centre suffered from gastroenteritis during the outbreak. Small round structured virus (SRSV) was detected in 4 of 8 stool specimens from sick persons. The school lunch contaminated by the infected food handler is the most probable source of this outbreak due to SRSV.