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The purpose of this study was to explore the variables related to paternal involvement in the caregiving of 6- to 8-year-old extremely low-birthweight (ELBW ) children, specifically, sociodem ographic factors related to the family or individual biological factors related to ELBW . Thirty-three children with a mean birthweight of 845.5 grams and a mean gestational age of 27.4 weeks participated in this research. Approximately 29% of their fathers were classified by the mothers as nonco-operative in overall child care. The paternal involvement in caregiving was related to the sociodemographic variables of the family; the co-operative fathers were proportionally m ore often from families where the child had no older female sibling(s) and/or grandparent(s), whereas the nonco-operative fathers were proportionally more often from families where the child had older female sibling(s) and/or grandparent(s). The individual perinatal risk variables and IQ, and the paternal variables (age, socioeconomic status) were not related to the paternal co-operativeness. Our sample mothers seemed to have raised their children in more difficult parenting and economic situations, and to have received proportionally more support from grandparent(s) than did typical Japanese mothers. The children's relationships with peers differed between the paternal co-operative and nonco-operative groups; there were proportionally more children from the nonco-operative group who preferred to play alone than to play with peer(s) at the ages of 3-5 years. Thus, scarce paternal involvement in the process of caregiving appeared to influence the children's sociability. [ABSTRACT FROM AUTHOR]

The article presents the study on the variation of insecticides in precipitation in the rural areas of Japan. Precipitation is an important mechanism of pesticide removal from the atmosphere and the distribution of pesticides in precipitation is important to evaluate their behaviors in the atmosphere as well as aquatic environment. A gas-chromatograph-mass spectrometer equipped with a fused-silica column was used for quantitative analysis. The sampling site for precipitation was located at a rural area in Niigata City in Japan as insecticides were sprayed by both aerial and ground application on these paddy fields. It has been found out that the insecticides increased in precipitation during and after the application periods accordingly their increase in the atmosphere.

The article presents a study which identifies the concentration levels of the volatile chlorinated hydrocarbons (VCH) and methyl chloroform (MCF) in ambient air at industrial areas in Japan. It was observed that some amounts of VCH are lost in the process and are introduced to the environment by some routes. MCF has been regulated in synthesis and usage because it is regarded as a responsible compound both for the stratospheric ozone depletion and the global warming. Researchers considered the meteorological factors winch are correlated with air temperature, flux of global solar radiation and duration of sunshine.

Aims/introduction: The time course of chronic kidney disease in young-onset type 2 diabetes mellitus remains unclear. We compared the trajectories of proteinuria and estimated glomerular filtration rate (eGFR) decline between young-onset (aged ≤40 years) and late-onset (aged >40 years) type 2 diabetes mellitus in a Japanese multicenter cohort., Materials and Methods: Participants without diabetic kidney disease were divided into two groups according to age at diagnosis: young- and late-onset. The primary endpoint was eGFR <60 mL/min/1.73 m 2 , proteinuria or both. Multivariable Cox proportional hazards were calculated to estimate incidence., Results: Among 626 participants with type 2 diabetes mellitus, 78 (12.4%) had young-onset and 548 (87.6%) had late-onset diabetes. The incidence of eGFR <60 mL/min/1.73 m 2 was lower (16.7% vs 33.5%, P = 0.003), but that of proteinuria was higher (46.2% vs 28.9%, P = 0.002) in the young-onset type 2 diabetes mellitus group. The Kaplan-Meyer curve showed that young-onset type 2 diabetes mellitus was associated with a decreased hazard ratio (HR) for eGFR <60 mL/min/1.73 m 2 and an increased HR for proteinuria compared with late-onset type 2 diabetes mellitus. In the multivariate Cox analysis, young-onset type 2 diabetes mellitus increased the HR (95% confidence interval) of proteinuria (1.53, 95% confidence interval 1.03-2.26), but did not change the eGFR <60 mL/min/1.73 m 2 HR., Conclusions: Young-onset type 2 diabetes mellitus has a lower HR of eGFR <60 mL/min/1.73 m 2 and an increased HR of proteinuria compared with late-onset type 2 diabetes mellitus, indicating that young-onset type 2 diabetes mellitus has a different time course for the development of proteinuria and subsequent eGFR decline., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background and Aim: Sodium picosulfate plus magnesium citrate (SP + MC) is a well-tolerated bowel preparation agent. However, Japan currently approves only two methods of taking SP + MC: the day-before and split-dose preparation, without approval of same-day preparations. This study aimed to evaluate the efficacy and safety of same-day SP + MC preparations., Methods: This was a multicenter, single-arm, nonrandomized, open-label study. We enrolled 145 Japanese patients between June and December 2023. The patients received two sachets of SP + MC dissolved in 300 ml of water and 1200 mL or more of clear liquid on the day of colonoscopy. Bowel cleansing efficacy, adverse events (AEs), and patient satisfaction were evaluated., Results: Of the enrolled patients, 137 underwent colonoscopy according to our protocol. Bowel preparation was adequate in 133 patients (97.1%). The mean total Boston Bowel Preparation Score was 8.3 ± 1.2. Five patients experienced AEs (3.6%): two (1.5%), abdominal pain; one (0.73%), ischemic enteritis; one (0.73%), vomiting or nausea; and one (0.73%), headache. All AEs were treated conservatively. None of the patients exhibited abnormal blood test results or clinical symptoms after receiving SP + MC. Regarding patient satisfaction, all patients were able to take SP + MC as directed; 136 (99.2%) expressed a preference for this bowel preparation for future colonoscopies., Conclusion: The same-day SP + MC preparation showed high bowel-cleansing efficacy and satisfaction in Japanese patients without serious AEs., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Evidence regarding chemosensitivity to different therapeutic regimens in epithelial ovarian cancer (EOC) remains limited. This study aimed to investigate EOC implementation in daily clinical practice and reveal favorable regimens for EOC among Japanese patients., Methods: We retrospectively collected clinical data of patients newly diagnosed with EOC from 2012 to 2021 at our affiliated institutions. We evaluated overall survival (OS) and progression-free survival (PFS) of conventional paclitaxel plus carboplatin (TC) vs. dose-dense TC (ddTC) according to the eligibility of GOG262 and JGOG3016 and those with bevacizumab (BEV) vs. without BEV based on GOG218. Further, we evaluated OS and PFS of ddTC and ddTC + BEV to TC + BEV among patients with stage III/IV., Results: The ddTC group (n = 402) demonstrated longer PFS and OS than the TC group (n = 165) (adjusted hazard ratios [aHRs] [95% confidential intervals (CIs)]: 0.69 [0.55-0.88] and 0.67 [0.50-0.90], respectively). The group with BEV (n = 158) demonstrated a longer PFS than those without BEV (n = 296) (0.74 [0.57-0.95]), but not for OS (0.84 [0.60-1.17]). The ddTC and ddTC + BEV groups (n = 259 and 117) demonstrated no statistically significant differences in PFS and OS than the TC + BEV group (n = 75) (1.09 [0.79-1.50] and 0.74 [0.52-1.08] for PFS and 0.89 [0.59-1.34] and 0.73 [0.50-1.05] for OS, respectively)., Conclusion: Our study may indicate ddTC, BEV, and their combination regimen as the promising first-line chemotherapy option among Japanese patients with advanced EOC., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: The applicability of ultra-hypofractionated (ultra-HF) whole-breast irradiation (WBI) remains unknown in Japanese women. This study aimed to evaluate the safety and efficacy of this approach among Japanese women and report the results of an interim analysis performed to assess acute adverse events (AEs) and determine whether it was safe to continue this study., Methods: We enrolled Japanese women with invasive breast cancer or ductal carcinoma in situ who had undergone breast-conserving surgery, were aged ≥ 40 years, had pathological stages of Tis-T3 N0-N1, and had negative surgical margins. Ultra-HF-WBI was delivered at 26 Gy in five fractions over one week. When the number of enrolled patients reached 28, patient registration was paused for three months. The endpoint of the interim analysis was the proportion of acute AEs of grade ≥ 2 (Common Terminology Criteria for Adverse Events v5.0) within three months., Results: Of the 28 patients enrolled from seven institutes, 26 received ultra-HF-WBI, and 2 were excluded due to postoperative infections. No AEs of grade ≥ 3 occurred. One patient (4%) experienced grade 2 radiation dermatitis, and 18 (69%) had grade 1 radiation dermatitis. The other acute grade 1 AEs experienced were skin hyperpigmentation (n = 10, 38%); breast pain (n = 4, 15%); superficial soft tissue fibrosis (n = 3, 12%); and fatigue (n = 1, 4%). No other acute AEs of grade ≥ 2 were detected., Conclusions: Acute AEs following ultra-HF-WBI were within acceptable limits among Japanese women, indicating that the continuation of the study was appropriate., (© 2024. The Author(s).)

Introduction: A remission induction therapy of granulocyte and monocyte adsorptive apheresis (GMA) was given to patients with Crohn's disease (CD). However, establishing an appropriate treatment strategy for GMA in patients with CD remains unclear., Methods: This study evaluated the clinical efficacy and subsequent clinical progression after GMA in patients with CD who underwent GMA in seven independent institutions in Japan from 2010 to 2023., Results: Sixteen patients were enrolled. The overall remission and response rates were 25.0% and 68.8%, respectively. All patients responding to GMA received biologics that were continuously used and 36.4% of patients remained on the same biologics 52 weeks after GMA. Notably, all patients who continued the same biologics had previously experienced a loss of response to biologics., Conclusion: GMA may exhibit effectiveness even in cases with refractory CD. Moreover, it represents a potential novel therapeutic option for refractory CD with loss of response to biologics., (© 2024 International Society for Apheresis and Japanese Society for Apheresis.)

Introduction: It remains unclear whether increased perirenal fat (PRF) accumulation is equally related to renal involvement in patients with and without diabetes mellitus (DM). We evaluated the association between PRF volume (PRFV) and low glomerular filtration rate (GFR) and proteinuria in people with or without type 2 diabetes mellitus (T2DM)., Research Design and Methods: We performed a cross-sectional analysis of 473 individuals without T2DM (non-DM, n=202) and with T2DM (DM, n=271). PRFV (cm 3 ), obtained from non-contrast CT, was indexed as PRF index (PRFV/body surface area, cm 3 /m 2 ). Multivariate-adjusted models were used to determine the ORs of PRFV and PRFV index for detecting estimated GFR (eGFR) decrease of <60 mL/min/1.73 m 2 proteinuria onset, or both., Results: Although body mass index (BMI), visceral fat area, and waist circumference were comparable between the non-DM and DM groups, kidney volume, PRFV, and PRFV index were higher in individuals with T2DM than in those without T2DM. In the multivariate analysis, after adjusting for age, sex, BMI, hypertension, smoking history, and visceral fat area ≥100 cm 2 , the cut-off values of PRFV index were associated with an eGFR<60 in individuals with DM (OR 6.01, 95% CI 2.20 to 16.4, p<0.001) but not in those without DM., Conclusions: PRFV is associated with low eGFR in patients with T2DM but not in those without T2DM. This suggests that PRF accumulation is more closely related to the onset and progression of diabetic kidney disease (DKD) than non-DKD. Clarifying the mechanisms through which PRF influences DKD development could pave the way for novel prevention and treatment strategies., 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.)

Purpose: The UK-FAST-Forward study showed that ultra-hypofractionated whole-breast irradiation (ultra-HF-WBI) involving five fractions of 26 Gy radiation over 1 week was not inferior to HF-WBI. However, it is not used in Japan due to safety concerns. In April 2022, we commenced a multi-institutional, single-arm, phase II trial. Our aim is to confirm the safety of ultra-HF-WBI after breast-conserving surgery (BCS) for breast cancer in Japanese women., Method: We plan to enroll 98 patients from 13 institutions. The primary endpoint is the proportion of late adverse events of grades ≥2 within 3 years., Discussion: We believe that this highly promising clinical study can positively impact the Japanese guidelines for breast cancer treatment. The results will help us decide whether or not ultra-HF-WBI can be used as a more convenient alternative to WBI., Registration Number and Date: This trial was registered in the UMIN Clinical Trials Registry (UMIN000047080) on March 4, 2022., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

In Japan, establishing a medical cooperation system for patients with inflammatory bowel disease (IBD) between IBD flagship and local care hospitals is a crucial task. Thus, this retrospective multicenter cohort study aims to examine the actual state of medical treatment in patients with IBD via a questionnaire survey administered to eight dependent institutes in Hokkaido, Japan. The present results clarified the clinical disparities of IBD treatment and hospital function between IBD flagship hospitals and local care hospitals. Moreover, the understanding level of IBD treatment in medical staff was significantly lower in local care than in IBD flagship hospitals. Furthermore, an abounding experience of IBD treatment affected the understanding level of IBD treatment of both medical doctors and staff. These findings indicate that selecting patients with IBD corresponding to disease activity, educational system for the current IBD treatment, and promotion of team medicine with multimedical staff can resolve clinical discrepancies between IBD flagship and local care hospitals. The IBD treatment inequities in Japan will be eliminated with the development of an appropriate medical cooperation system between IBD flagship and local care hospitals.

Context: Previous studies have assessed the usefulness of data-driven clustering for predicting complications in patients with diabetes mellitus. However, whether the diabetes clustering is useful in predicting sarcopenia remains unclear., Objective: To evaluate the predictive power of diabetes clustering for the incidence of sarcopenia in a prospective Japanese cohort., Design: Three-year prospective cohort study., Setting and Patients: We recruited Japanese patients with type 1 or type 2 diabetes mellitus (n = 659) between January 2018 and February 2020 from the Fukushima Diabetes, Endocrinology, and Metabolism cohort., Interventions: Kaplan-Meier and Cox proportional hazards models were used to measure the predictive values of the conventional and clustering-based classification of diabetes mellitus for the onset of sarcopenia. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia (AWGS) 2019 consensus update., Main Outcome Measures: Onset of sarcopenia., Results: Cluster analysis of a Japanese population revealed 5 diabetes clusters: cluster 1 [severe autoimmune diabetes (SAID)], cluster 2 [severe insulin-deficient diabetes (SIDD)], cluster 3 (severe insulin-resistant diabetes, cluster 4 (mild obesity-related diabetes), and cluster 5 (mild age-related diabetes). At baseline, 38 (6.5%) patients met the AWGS sarcopenia criteria, and 55 had newly developed sarcopenia within 3 years. The SAID and SIDD clusters were at high risk of developing sarcopenia after correction for known risk factors., Conclusions: This study reveals that among the 5 diabetes clusters, the SAID and SIDD clusters are at a high risk for developing sarcopenia. Clustering-based stratification may be beneficial for predicting and preventing sarcopenia in patients with diabetes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Study Aims: Gastric adenocarcinoma of fundic-gland type (GA-FG) was first proposed as a new entity of gastric adenocarcinoma in 2010. Subsequently, gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM) was reported as a subtype of gastric adenocarcinoma. This study aimed to investigate the endoscopic findings of GA-FGM and to evaluate the differences between GA-FGM and GA-FG., Patients and Methods: This was a single-center retrospective study. Participants were selected from patients with gastric cancer treated at Fukuoka University Chikushi Hospital, between September 2007 and May 2020. Patients histologically diagnosed with GA-FGM or GA-FG were enrolled, and endoscopic findings were analyzed in detail., Results: A total of 12 GA-FGM lesions (12 patients) and 14 GA-FG lesions (13 patients) were analyzed. The two lesion types showed similar features: most lesions were of elevated type, located in the upper stomach, and developed in the stomach without Helicobacter pylori infection. On conventional endoscopy using the dye-spraying method, well-demarcated fine granular areas were observed in 7 GA-FGM lesions (58%) but not in any GA-FG lesions, with a significant difference between the two groups (P = 0.001). Magnifying endoscopy with narrow-band imaging (NBI) showed that 11 GA-FGM lesions (92%) met the diagnostic criteria for cancer according to the vessel plus surface classification system, whereas none of the GA-FG lesions met the same criteria (0%, 0/14) (P = 0.001)., Conclusion: Our results suggest that magnifying endoscopy with NBI is a potentially useful method for the diagnosis of GA-FGM., (© 2021. The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

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.)

Background: Microvascular decompression (MVD) is the most effective procedure for hemifacial spasm (HFS). MVD results from nonspecialized or low-volume institutes are not always reliable. Most studies on MVD for HFS are retrospective and single centered; to the best of our knowledge, no prospective, multicenter studies exist., Objective: To evaluate short- and long-term outcomes and complications in patients who underwent MVD for HFS in specialized Japanese institutions, in this multicenter, prospective, cohort study., Methods: Included patients had undergone MVD for HFS in study centers between April 2012 and March 2015. Patients' postoperative grade of involuntary movements and complications were recorded postoperatively at 7 d (short-term) and at 1 (mid-term) and 3 (long-term) yr., Results: A total of 486 patients (150 men, 336 women; mean age 53.9 yr with 181 patients over 60 yr) were enrolled during the study period. Neuromonitoring was used in 96.3% of the cases. The complete cure rate of symptom relief, mortality rate, and complication rate at short-term follow-up were 70.6%, 0%, and 15%, respectively. The long-term follow-up was completed by 463 patients (95.3%); the complete cure rate of symptom relief and complication rate were 87.1% and 3.0%, respectively., Conclusion: Our study revealed that under expert guidance and intraoperative neuromonitoring, the long-term curative effect rate of MVD for HFS is high, while complications are uncommon and usually transient. Our results indicate that MVD is an effective and safe treatment for patients with HFS, including elderly patients., (© Congress of Neurological Surgeons 2021.)

Background: Current guidelines recommend early termination of triple therapy and the use of direct oral anticoagulants (DOAC) for non-valvular atrial fibrillation (NVAF) patients who undergo percutaneous coronary intervention (PCI), due to safety concerns. However, to date, real-world medication usage and safety outcomes (specifically bleeding) in NVAF patients with stent implantation have not been well assessed., Methods: This was a retrospective, observational, medical database cohort study in Japanese ischemic heart disease (IHD) patients with NVAF who underwent PCI between 2012 and 2017. The primary outcome was clinically relevant bleeding; secondary outcomes included individual bleeding events. A multivariate analysis was conducted to identify risk factors affecting the occurrence of clinically relevant bleeding events., Results: The analysis population comprised 5695 patients [3530 received DOACs and 2165 received vitamin K antagonists (VKAs)]. The incidence of primary outcome events (clinically relevant bleeding/100 patient-years) was 6.05 in the DOAC group and 8.42 in the VKA group, resulting in a nonsignificant 21% lower risk in the DOAC group. The DOAC group also had a nonsignificant 24%, 24%, and 34% lower risk of bleeding requiring transfusion, intracranial bleeding, and lower gastrointestinal bleeding, respectively, compared with the VKA group. A multivariate analysis of the primary outcome showed a significantly higher risk of bleeding among older patients and those with lower body weight and abnormal renal function., Conclusions: In this retrospective real-world evaluation of IHD patients with NVAF and PCI, DOAC-treated patients had a lower risk of developing clinically relevant bleeding compared with the VKA group., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Extravasation incidence is exceptionally low; however, ulceration or necrosis occurs in severe cases, possibly requiring surgical treatment. Early extravasation signs and symptoms are not always evident on treatment day, and inflammation, which leads to ulceration or necrosis, may appear several days later. Therefore, to minimize damage, identification of high-risk groups is required. This study aims to investigate the relationship between subcutaneous edema which is an early extravasation sign, and skin surface temperature using a thermosensitive liquid crystal film., Methods: Patients receiving chemotherapy through a peripheral intravenous catheter were recruited. Subcutaneous tissue around the catheterization site was observed for the presence of subcutaneous edema by ultrasonography. During chemotherapy initiation, a thermosensitive liquid crystal film was placed on the catheterization site. Color changes of the film were observed, and each case was classified according to low-temperature distribution patterns. To investigate the factors associated with temperature distribution pattern, logistic regression analysis was performed using clinically selected independent variables., Results: Data from 63 patients were analyzed. No obvious extravasation was observed. Film analysis revealed 34 cases of broadening low-temperature area from the vein and 23 cases of non-broadening low-temperature area from the vein. Subcutaneous edema was observed in 18 patients: 17 with broadening low-temperature area from the vein and 1 with non-broadening low-temperature area from the vein. Subcutaneous edema was positively correlated with broadening low-temperature area from the vein., Conclusion: Catheter site skin temperature distribution pattern during chemotherapy was associated with subcutaneous edema which is the early extravasation sign immediately after chemotherapy., (Copyright © 2020. Published by Elsevier Ltd.)

Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene have been reported with different clinical phenotypes including Silver syndrome (SS)/spastic paraplegia 17 (SPG17), distal hereditary motor neuropathy type V (dHMN-V), and Charcot-Marie-Tooth (CMT) disease type 2. We screened 407 Japanese patients who were clinically suspected of having CMT by exome sequencing and searched mutations in BSCL2. As a result, we identified five patients with heterozygous mutations in BSCL2. We confirmed three cases of known mutations (p.N88S and p.S90L) and two cases of novel mutations (p.N88T and p.S141A). The clinical features of the cases with known mutations in Japan were similar to those previously reported in other countries. In particular, there were many cases with sensory disturbance. The case with p.N88T mutation showed severe phenotype such as early onset age and prominent vocal cord paresis. The case with p.S141A mutation showed characteristics of demyelinating neuropathy such as CMT disease type 1 by electrophysiological examination. In this article, we report the clinical features and spread of cases with BSCL2 mutation in a Japanese cohort., (© 2020 Peripheral Nerve Society.)

Aims: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is performed safely and effectively in elderly patients; however, whether ESD for EGC in elderly patients with frailty is safe and improves prognosis remains unclear., Methods: In total, 142 patients aged ≥80 years who underwent ESD for EGC between September 2008 and September 2014 were included. We compared outcomes between patients with frailty and those without frailty. Frailty was assessed using the Clinical Frailty Scale (CFS) based on a patient's status before admission. Study endpoints were short- and long-term clinical outcomes after ESD., Results: Patients were allocated into two groups: no frailty (CFS 1-3, n = 101) versus frailty (CFS 4-7, n = 41). Short-term clinical outcomes, specifically, adverse events and curability, did not differ between the two groups. For the long-term clinical outcomes, patients with frailty had significantly worse outcomes after ESD than those without frailty (the 3-year overall survival rates were 73.2% vs. 93.1%; P < 0.001 with log-rank test). The Cox proportional hazards model showed that frailty was only an independent risk factor for poor prognosis., Conclusions: ESD for EGC is safe for elderly patients with or without frailty. However, elderly patients with frailty have a significantly poorer prognosis than those without frailty after ESD. Our results indicate that the frailty evaluation may be helpful to determine whether ESD for EGC should be performed. Geriatr Gerontol Int 2020; 20: 461-466., (© 2020 Japan Geriatrics Society.)

Aims/introduction: Gut microbiota have various effects on human health. Some previous reports have shown that gut microbiota change during pregnancy and affect metabolism, but others have shown that microbiota do not change. Here, we examined the gut microbiota and glycoalbumin levels of 45 healthy Japanese women during pregnancy., Materials and Methods: We carried out 16S rRNA gene sequencing analyses of maternal stool samples and compared the gut microbiota composition of samples from women in early and late pregnancy. We also examined the association between gut microbiota and maternal characteristics, including glycoalbumin., Results: Microbiota composition in early and late pregnancy did not differ, according to principal coordinate analysis of weighted and unweighted UniFrac distances. Shannon indices were not different between early and late pregnancy. The proportion of one phylum, TM7, significantly decreased in late pregnancy compared with early pregnancy, but the proportions of other major phyla did not change. The Shannon index of late pregnancy was negatively associated with pregestational body mass index and positively correlated with glycoalbumin level, with adjustment of covariates., Conclusions: We concluded that Japanese women did not show obvious differences in gut microbiota during pregnancy, except for TM7, and that the diversity of gut microbiota might affect maternal metabolism. As this study had limited statistical power, further large-scale studies are required., (© 2019 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objective: To investigate the characteristics of materials used as prostheses for microvascular decompression surgery (MVDs) in Japan and their possible adverse events (AEs) to determine preferable materials for MVDs., Methods: A questionnaire was sent to all members of the Japanese Society for MVDs, and answers were obtained from 59 institutions., Results: Among a total of 2789 MVDs, 1088 operations for trigeminal neuralgia, 1670 for hemifacial spasm, and 31 others, including 117 reoperations, were performed between April 2011 and March 2014. Nonabsorbable material was used in 96.5% of MVDs, including polytetrafluoroethylene (PTFE) (80.5%), polyurethane (11.9%), expanded PTFE (2.1%), and silk thread (1.47%). The use of absorbable materials, including fibrin glue (87.5%), cellulose (13.5%), gelatin (4,77%), and collagen (1.76%), was reported. The major combinations were PTFE with fibrin glue (58.7%) followed by PTFE alone (7.60%). Eighty-eight AEs in 85 (3.2%) cases were reported among 2672 first operations. AEs included 51 central nervous system dysfunctions, 15 wound infections/dehiscence, and 10 others, which were presumed to be related to the intraoperative procedure. Among relatively high-, moderate-, and low-volume centers, there were no significant differences in the frequency of AEs (P = 0.077). Tissue-prosthesis adhesion and/or granuloma formation were reported in 13 cases of 117 reoperations. The incidence of adhesion-related recurrence was 11.1% of all reoperations., Conclusions: The number of AEs was quite low in this survey, and intradural use of any prosthesis reported in this paper might be justified; however, further development of easily handled and less-adhesive prosthesis materials is awaited., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Maternal exposure to polychlorinated biphenyls (PCBs) results in abnormal fetal development, possibly because of epigenetic alterations. However, the association between PCB levels in cord serum with fetal DNA methylation status in cord tissue is unclear. This study aims to identify alterations in DNA methylation in cord tissue potentially associated with PCB levels in cord serum from a birth cohort in Chiba, Japan (male neonates = 32, female neonates = 43). Methylation array analysis identified five sites for female neonates (cg09878117, cg06154002, cg06289566, cg12838902, cg01083397) and one site for male neonates (cg13368805) that demonstrated a change in the methylation degree. This result was validated by pyrosequencing analysis, showing that cg06154002 ( tudor domain containing 9 : TDRD9 ) in cord tissue from female neonates is significantly correlated with total PCB levels in cord serum. These results indicate that exposure to PCBs may alter TDRD9 methylation levels, although this hypothesis requires further validation using data obtained from female neonates. However, since the present cohort is small, further studies with larger cohorts are required to obtain more data on the effects of PCB exposure and to identify corresponding biomarkers.

Precis: Wider area bleb revision using bleb knife with adjunctive mitomycin C (MMC) had a good success rate, according to strict success criteria, except in patients with neovascular glaucoma (NVG)., Purpose: We determined the efficacy of wider area bleb revision after filtering surgery using bleb knife with adjunctive MMC., Patients and Methods: In this retrospective single-center study, we analyzed 86 patients with glaucoma (46 primary open-angle, 18 exfoliations, 13 secondary, and 9 neovascular) after bleb revision using bleb knife with adjunctive MMC after a minimum follow-up of 6 months. A Kaplan-Meier survival analysis with log-rank tests and Cox proportional hazards regression analyses were performed. The main outcome measure was a successful initial bleb revision using bleb knife with adjunctive MMC, arbitrarily defined as intraocular pressure (IOP) control <15 mm Hg without any IOP-lowering medication, additional bleb revision, or glaucoma surgery., Results: The mean time since the initial filtering surgery was 243.8 days, and the mean prebleb revision IOP was 22.0±4.8 mm Hg. The total cumulative success rate of the bleb revision using bleb knife with MMC was 49% at 6 months and 30% at 1 year. Patients with primary open-angle glaucoma had the best success rate (64% at 6 mo and 40% at 1 y). Log-rank tests revealed that patients with NVG had the worst prognosis (P<0.01). NVG was the only significant risk factor identified for short survival time (odds ratio, 167.10; 95% confidence interval, 1.78-15620.44; P=0.027)., Conclusion: Wider area bleb revision using bleb knife with adjunctive MMC had a good success rate, according to strict success criteria, except in patients with NVG.

Objective: Recently, we established new histopathological subtypes of high-grade serous ovarian cancer (HGSOC) that include the mesenchymal transition (MT) type, the immune reactive (IR) type, the solid and proliferative (SP) type and the papillo-glandular (PG) type. Furthermore, we identified that the mesenchymal transcriptome subtype might be sensitive to taxane. We investigated whether these different histopathological subtypes of HGSOC require individualized chemotherapy for optimal treatment., Methods: We conducted the Japanese Gynecologic Oncology Group (JGOG) 3016A1 study, wherein we collected hematoxylin and eosin slides (total n = 201) and performed a histopathological analysis of patients with HGSOC registered in the JGOG3016 study, which compared the efficacy of conventional paclitaxel and carboplatin (TC) and dose-dense TC (ddTC). We analyzed the differences in progression-free survival (PFS) and overall survival (OS) among the four histopathological subtypes. We then compared the PFS between the TC group and the ddTC group for each histopathological subtype., Results: There were significant differences in both PFS and OS among the four histopathological subtypes (p = 0.001 and p < 0.001, respectively). Overall, the MT subtype had the shortest PFS (median 1.4 y) and OS (median 3.6 y). In addition, the MT subtype had a longer PFS in the ddTC group (median 1.8 y) than in the TC group (median 1.2 y) (p = 0.01). Conversely, the other types had no significant difference in PFS when the two regimens were compared., Conclusions: The MT type of HGSOC is sensitive to taxane; therefore, the ddTC regimen is recommended for this histopathological subtype., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Favus is a type of dermatophytosis known to produce yellow scutula around hair follicles. Most cases of this disease worldwide are infections of Trichophyton schoenleinii. Favus has rarely been reported in Japan throughout the last four decades, and T. schoenleinii has not been clinically isolated in any case during the period. Here, we report a case of favus of vellus hair observed in a 63-year-old Japanese woman. Fungal culture showed negative; however, we detected fungal elements in the crust and hair bulbs by Grocott staining. Pathogenic fungi were identified as T. schoenleinii by polymerase chain reaction-based DNA sequencing, targeting the internal transcribed spacer regions of the rRNA gene using the formalin-fixed, paraffin-embedded tissue sample. She was successfully treated with p.o. administration of terbinafine and topical application of luliconazole cream., (© 2019 Japanese Dermatological Association.)

Background: Venous thromboembolism (VTE) has been shown to be more frequent in inflammatory bowel disease (IBD) than in the general population in Western studies. However, the actual state of VTE in Asian IBD remains poorly understood., Aims: To reveal the incidence of VTE in IBD patients in Japan., Methods: Eighty-five patients admitted to 3 gastroenterology centers were registered from 2013 to 2018. The incidence of VTE in patients with IBD (n = 42) was prospectively compared to that among patients with other digestive diseases (n = 43). The presence of VTE was surveyed using contrast-enhanced computed tomography and/or ultrasonography at admission and at 1-2 weeks after admission. The patient characteristics and laboratory data of IBD patients with or without VTE were compared to determine the risk factors for VTE., Results: The incidence of VTE with IBD was 16.7%, which was significantly more frequent than with other digestive diseases (2.3%; p = 0.0296). In IBD patients, VTE was detected in 6 of 22 patients with ulcerative colitis (27.2%) but in only 1 of 20 patients with Crohn's disease (5.0%). VTE was diagnosed at admission in 4 IBD patients and 2 weeks after admission in 3 IBD patients. The risk factors of VTE in IBD were the presence of an indwelling central venous catheter, a low level of total protein, a low activated partial thromboplastin time, and a high level of fibrinogen degradation products., Conclusion: VTE was frequently detected in Japanese IBD patients both at and after admission. Adequate screening and prophylaxis for VTE is deemed necessary in IBD., (© 2018 S. Karger AG, Basel.)

Background: In this study, survival and cause of death were investigated in patients with Crohn's disease (CD) at a tertiary referral center., Methods: A database was created based on the medical records of 1108 CD patients who had a history of visiting our hospital to investigate background characteristics, cumulative survival rates from diagnosis, causes of death, and the standardized mortality ratio (SMR) for each cause of death. A follow-up questionnaire survey of patients followed up inadequately was also conducted. The cumulative survival rate from diagnosis was determined using the life table method and compared with that of a sex- and age-matched population model from the year 2000., Results: The study included 1108 patients whose mean age at diagnosis was 25.6 ± 10.8 years. The mean duration of follow-up was 14.6 ± 9.4 years, and there were 52 deaths. The cumulative survival rate was significantly lower 25 years after the diagnosis of CD (91.7%) than in the standard population model (95.7%). SMRs for both all causes [3.5; 95% confidence interval (CI): 2.7-4.6] and CD-specific causes (36.7; 95% CI 26.1-51.6) were high. Among the CD-specific causes, SMRs were especially high for small intestine and colorectal cancers, gastrointestinal diseases including intestinal failure (IF), perioperative complications, and amyloidosis., Conclusion: The SMRs for both all causes and CD-specific causes were high in CD patients. CD-specific causes including intestinal cancer, IF, perioperative complications, and amyloidosis showed especially high SMRs.

Objective: Since there have been few large series studies to date, we investigated the relationship between Trousseau's syndrome associated with cerebral infarction and its clinical associations with ovarian cancer., Methods: In this study, we investigated the association between cerebral infarction onset and ovarian cancer. Eight-hundred twenty-seven consecutive ovarian cancer patients from 4 affiliated academic institutions were included in the study over a 12 years period. All patients were histopathologically diagnosed as epithelial ovarian cancer and were analyzed retrospectively., Results: The 27 patients (3.2%) presented with cerebral infarction during the study period, 14 patients onset prior to treatment (1.7%), and 13 patients onset after start of initial treatment (1.5%). Univariate analysis and multivariate analysis was performed for onset of Trousseau's syndrome and various clinical and pathological parameters. There was no statistical significance between the occurrence of Trousseau's syndrome with age or International Federation of Gynecology and Obstetrics (FIGO) stage; however, univariate analysis and multivariate analysis demonstrated a statistically significant association between clear cell carcinoma (CCC) and non-CCC histology., Conclusion: Thus, our results demonstrate that Trousseau's syndrome with cerebral infarction occurred with greater incidence among CCC cases compared to non-CCC cases., Competing Interests: None of the authors have any conflict of interest to disclose., (Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Mutations in small heat shock protein beta-1 (HspB1) have been linked to Charcot-Marie-Tooth (CMT) disease type 2F and distal hereditary motor neuropathy type 2B. Only four cases with HSPB1 mutations have been reported to date in Japan. In this study between April 2007 and October 2014, we conducted gene panel sequencing in a case series of 1,030 patients with inherited peripheral neuropathies (IPNs) using DNA microarray, targeted resequencing, and whole-exome sequencing. We identified HSPB1 variants in 1.3% (13 of 1,030) of the patients with IPNs, who exhibited a male predominance. Based on neurological and electrophysiological findings, seven patients were diagnosed with CMT disease type 2F, whereas the remaining six patients were diagnosed with distal hereditary motor neuropathy type 2B. P39L, R127W, S135C, R140G, K141Q, T151I, and P182A mutations identified in 12 patients were described previously, whereas a novel K123* variant with unknown significance was found in 1 patient. Diabetes and impaired glucose tolerance were detected in 6 of the 13 patients. Our findings suggest that HSPB1 mutations result in two phenotypes of inherited neuropathies and extend the phenotypic spectrum of HSPB1-related disorders., (© 2018 The Authors. Journal of the Peripheral Nervous System published by Wiley Periodicals, Inc. on behalf of Peripheral Nerve Society.)

Background: Eradication therapies for Helicobacter pylori infection are advancing as new acid inhibitory reagents approved. The aim of this study was to assess the efficacy and safety of vonoprazan-based triple treatment., Materials and Methods: Triple therapy with vonoprazan and two antibiotics (amoxicillin and clarithromycin or metronidazole) received focus in this analysis. We performed a multicenter retrospective study of patients who received vonoprazan-based eradication therapy between February 2015 and February 2016 and conducted a review of the literature., Results: The eradication rate among the 799 patients in our multicenter study was 94.4% (95% confidence interval [CI] 92.6-96.2%) in the per-protocol analysis for first-line treatment (with vonoprazan 20 mg, amoxicillin 750 mg, and clarithromycin 200 or 400 mg, twice a day for 7 days) and 97.1% (95% CI 93.0-101.1%) for second-line treatment (with vonoprazan 20 mg, amoxicillin 750 mg, and metronidazole 250 mg, twice a day for 7 days). The overall incidence of adverse events was 4.4% in an intention-to-treat analysis with no patients hospitalized. In a literature review, six reports, in which 1380 patients received vonoprazan-based first-line eradication therapy, were included and were all reported by Japanese researchers. The eradication success rates in per-protocol analysis were between 85 and 93%, which was roughly the same among the studies., Conclusions: Vonoprazan-based triple therapy was effective and safe for Helicobacter pylori eradication in real-world experience, confirmed by a multicenter study and a review of the pertinent literature.

Objective: The objective of this study was to identify new causes of Charcot-Marie-Tooth (CMT) disease in patients with autosomal-recessive (AR) CMT., Methods: To efficiently identify novel causative genes for AR-CMT, we analyzed 303 unrelated Japanese patients with CMT using whole-exome sequencing and extracted recessive variants/genes shared among multiple patients. We performed mutation screening of the newly identified membrane metalloendopeptidase (MME) gene in 354 additional patients with CMT. We clinically, genetically, pathologically, and radiologically examined 10 patients with the MME mutation., Results: We identified recessive mutations in MME in 10 patients. The MME gene encodes neprilysin (NEP), which is well known to be one of the most prominent beta-amyloid (Aβ)-degrading enzymes. All patients had a similar phenotype consistent with late-onset axonal neuropathy. They showed muscle weakness, atrophy, and sensory disturbance in the lower extremities. All the MME mutations could be loss-of-function mutations, and we confirmed a lack/decrease of NEP protein expression in a peripheral nerve. No patients showed symptoms of dementia, and 1 patient showed no excess Aβ in Pittsburgh compound-B positron emission tomography imaging., Interpretation: Our results indicate that loss-of-function MME mutations are the most frequent cause of adult-onset AR-CMT2 in Japan, and we propose that this new disease should be termed AR-CMT2T. A loss-of-function MME mutation did not cause early-onset Alzheimer's disease. Identifying the MME mutation responsible for AR-CMT could improve the rate of molecular diagnosis and the understanding of the molecular mechanisms of CMT., (© 2016 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Gambling disorder is a psychiatric disorder characterized by persistent and recurrent problematic gambling behavior, associated with impaired functioning, reduced quality of life, and frequent divorce and bankruptcy. Gambling disorder is reclassified in the category Substance-Related and Addictive Disorders in the DSM-5 because its clinical features closely resemble those of substance use disorders, and gambling activates the reward system in brain in much the same way drugs do. Prevalence of gambling disorder in Japan is high rate because of slot machines and pachinko game are very popular in Japan. The author recommend group psychotherapy and self-help group (Gamblers Anonymous), because group dynamics make them accept their wrongdoings related to gambling and believe that they can enjoy their lives without gambling.

Functional mitral regurgitation (FMR) is a common and critical condition in patients with heart failure (HF); however, the prevalence and clinical outcome of FMR in Japanese real-world clinical practice remain unclear. Within a single hospital-based cohort in the Shinken Database 2004-2011, which comprised all new patients (n = 17,517) who visited the Cardiovascular Institute, we followed symptomatic HF patients. A total of 1,701 patients were included: 104 FMR patients (who had moderate to severe FMR) and 1,597 non-FMR patients (who had none or mild FMR). FMR patients had lower rates of hypertension and dyslipidemia, but higher rates of dilated cardiomyopathy, atrial fibrillation, and New York Heart Association functional class III/IV. FMR patients had higher levels of brain natriuretic peptide and lower left ventricular function. Use of cardiovascular drugs was more common among FMR patients. Kaplan-Meier curves revealed that the incidences of all-cause death, cardiovascular death, and admission for HF were significantly higher in FMR patients. The adjusted Cox regression analysis showed that significant FMR was associated with higher incidences of all-cause death [hazard ratio (HR) 2.179, 95 % confidence interval (CI) 1.266-3.751; P = 0.005], cardiovascular death (HR 2.371, 95 % CI 1.157-4.858; P = 0.018), and admission for HF (HR 1.819, 95 % CI 1.133-2.920; P = 0.013). FMR was common in Japanese symptomatic HF patients and was associated with adverse long-term outcomes. Establishing optimal therapeutic strategies for FMR is warranted.

Frequent supraventricular extrasystoles (SVEs) are associated with the subsequent first-time appearance of atrial fibrillation (AF) and ischemic stroke. The aim of this study was to investigate the combined role of SVEs and an AF-related risk score for ischemic stroke, the CHADS2 score, on the occurrence of new AF in patients in sinus rhythm. The Shinken Database 2004-2010 lists 3,263 patients who underwent 24-hour Holter monitoring. A total of 2,589 patients were analyzed, after excluding 674 patients previously diagnosed with AF. Frequent SVEs were defined as ≥102 beats/day (the top quartile) and the presence of a clinical background for a CHADS2 score ≥2 points as a high CHADS2 score. During the mean follow-up period of 571.4 ± 606.4 days, new AF occurred in 38 patients (9.4 per 1,000 patient-years). The incidence of new AF was 2.7 and 37.7 per 1,000 patient-years for patients with nonfrequent SVEs (<102 beats/day) and low CHADS2 scores and those with frequent SVEs and high CHADS2 scores, respectively. Multivariate Cox regression analysis showed that the hazard ratio for frequent SVEs and a high CHADS2 score compared with nonfrequent SVEs and a low CHADS2 score was 9.49 (95% confidence interval 3.20 to 28.15, p <0.001), even after adjustment for gender, age, medications, and echocardiographic parameters. In conclusion, frequent SVEs and a high CHADS2 score independently and synergistically predict the first-time appearance of AF in patients in sinus rhythm, indicating an approximately 10-fold higher risk. Patients meeting these criteria should have more aggressive early intervention for preventing AF., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To evaluate the incidence of complications of intrathecal baclofen (ITB) therapy for spasticity in Japan, where a unique training course and nationwide registration are required., Materials and Methods: An analysis of complications was performed in all patients who underwent ITB in Japan from 2005 to 2011. Prior to surgery, all the doctors involved took a one-day training course, which included hands-on training. Surgical techniques that avoided complications were emphasized., Results: A total of 406 pumps were implanted in 400 patients (277 men, 123 women) having severe spasticity. Because this study is currently in progress, among the 400 patients, 78.3% (313/400) had finished a one-year observation follow-up. There were 369 adult and 31 juvenile (under 17 years old) patients, including 12 patients under nine years old. All-cause adverse events were seen in 148 patients (37%), and 93 (23.3%) of these were regarded as severe. Catheter problems were observed in 34 (8.5%) patients: catheter migration in 25 (6.3%), breakage in 6 (1.5%), obstruction in 2 (0.5%), kinking in 1 (0.3%), and dislodgement in 1 (0.3%). Pump trouble was observed in seven (1.8%) patients: alarm abnormality in one (0.3%), memory error in one (0.3%), delayed recovery in one (0.3%), rotation in one (0.3%), malfunction in one (0.3%), and abnormal infusion rate in two (0.6%). Device-related and surgical wound infection occurred in 12 patients (3%), and nine were regarded as severe. Leakage or subcutaneous accumulation of the cerebrospinal fluid was seen in 13 patients (3.3%)., Conclusion: The requirement of taking of a training course before starting ITB seemed to reduce complications. Although there were surgery-related complications, the rate of complications in Japan appeared to be lower than those reported in larger series of ITB. However, whether the reported rates can be primarily ascribed to a mandatory training course requires further investigations., (© 2012 International Neuromodulation Society.)

Background: Tobacco smoking is a well-known risk factor for cardiovascular disease, but controversial results have been reported regarding its relationship with atrial fibrillation (AF). Moreover, no study on the relationship between smoking and AF has yet been undertaken in a Japanese context., Methods and Results: We used data from the Shinken Database 2004-2011 (men/women, n=10,714/6,803, respectively), which included all new patients attending the Cardiovascular Institute between June 2004 and March 2012. AF was diagnosed in 1,698 and 598 men and women, respectively. In men, smokers were more prevalent in the AF than in the non-AF group (54.5% vs. 44.7%), whereas in women the prevalence of smokers was similar between AF and non-AF groups (14.4% vs. 15.4%). This discrepancy between the sexes seems to derive from a characteristic distribution pattern of smoking habit in women. After adjustment for various cofactors, smoking was independently associated with AF (odds ratio 1.54; 95% confidence interval 1.35-1.75; P<0.001) without a significant interaction between sex categories (P=0.195)., Conclusions: Smoking was independently associated with AF without a significant interaction between sex categories among Japanese patients visiting a cardiovascular hospital. Further studies using a prospective cohort design are required to confirm a causal link between smoking and AF in Japanese patients.

Background: Some patients under close colonoscopic surveillance still develop colorectal cancer, thus suggesting the overlook of colorectal adenoma by endoscopists. AFI detects colorectal adenoma as a clear magenta, therefore the efficacy of AFI is expected to improve the detection ability of colorectal adenoma. The aim of this study is to determine the efficacy of AFI in detecting colorectal adenoma., Methods: This study enrolled 88 patients who underwent colonoscopy at Asahikawa Medical University and Kushiro Medical Association Hospital. A randomly selected colonoscopist first observed the sigmoid colon and rectum with conventional high resolution endosopy (HRE). Then the colonoscopist changed the mode to AFI and handed to the scope to another colonoscopist who knew no information about the HRE. Then the second colonoscopist observed the sigmoid colon and rectum. Each colonoscopist separately recorded the findings. The detection rate, miss rate and procedural time were assessed in prospective manner., Results: The detection rate of flat and depressed adenoma, but not elevated adenoma, by AFI is significantly higher than that by HRE. In less-experienced endoscopists, AFI dramatically increased the detection rate (30.3%) and reduced miss rate (0%) of colorectal adenoma in comparison to those of HRE (7.7%, 50.0%), but not for experienced endoscopists. The procedural time of HRE was significantly shorter than that of AFI., Conclusions: AFI increased the detection rate and reduced the miss rate of flat and depressed adenomas. These advantages of AFI were limited to less-experienced endoscopists because experienced endoscopists exhibited a substantially high detection rate for colorectal adenoma with HRE.

We investigated mid-term outcomes after ring annuloplasty with the MC3 ring and aimed to identify factors associated with recurrent tricuspid regurgitation (TR). From October 2006 to October 2010, 136 patients (male:female 80:56, with a mean age 64.7±11.8 years) underwent tricuspid valve (TV) annuloplasty for functional TR. The indications for TV annuloplasty were (1) severe TR, or (2) mild or moderate TR with pulmonary hypertension (systolic pulmonary artery pressure >50 mmHg) or tricuspid annular (TA) dilatation, in patients undergoing mitral valve (MV) surgery. The average follow-up period was 1.5±0.8 years. The overall survival rates were 97.1±0.15%, 93.4 ± 0.02% and 90.7 ± 0.28% at three months, one year and four years, respectively. Freedom from recurrent moderate TR was 98.5±0.01, 95.6 ± 0.17% and 90.6 ± 0.03% at three months, one year and four years, respectively. Multivariate analysis revealed that residual TR was significantly associated with preoperative severe TR, left ventricular end-diastolic dimension >70 mm, right ventricular dimension >40 mm, dilated cardiomyopathy (DCM) and left ventriculoplasty. This MC3 ring corrects TR effectively, and provided good results. We must point out, however, that additional or alternative surgical options should still be considered for high-risk of repair failure, such as those with DCM or high pulmonary hypertension.

Background: To prevent a future shortage of cardiologists, it is important for female cardiologists to continue working. Gender differences in the professional and private lives of cardiologists, as well as the barriers to work for female cardiologists, were surveyed., Methods and Results: In August 2007, a questionnaire was mailed to all 195 faculty members/fellows and 155 alumni of the Department of Cardiovascular Medicine at Nippon Medical School. More female cardiologists were dissatisfied with their job than male cardiologists (34% vs 17%, P<0.005). Women reported greater career limitation by family responsibilities and housework. Men and women both reported that long working hours was the most problematic issue, but significantly more women reported this than men (76% vs 94%, P<0.05). Female cardiologists were more concerned about occupational radiation exposure (88% vs 59%, P<0.01) and wanted opportunities for retraining after childcare leave (100% vs 76%, P<0.01)., Conclusions: The following measures should be taken: (1)establishment of more family-friendly working conditions in hospitals, (2)provision of various work positions that allow more flexibility and predictability for women, (3)establishment of a retraining system, and (4)development of work and research opportunities that are attractive to women. The Japanese Circulation Society is expected to establish a retraining system at certified institutions.

Aims: Intestinal metaplasia is considered to be a precursor lesion in both Barrett's and intestinal-type gastric cancer. The aim was to clarify the differences in molecular pathology between specialized intestinal metaplasia (SIM) in Barrett's oesophagus (BO), cardiac (CIM) and gastric intestinal metaplasia (GIM)., Methods and Results: Eighty-eight SIM cases with BO, 30 CIM cases and 52 GIM cases in patients with or without Helicobacter pylori infectionwere analysed for genetic instability and Das-1. Microsatellite instability and a loss of heterozygosity were evaluated at five microsatellite loci. The incidence of genetic instability was 55.7% in SIM, 40.0% in CIM and 23.1% in GIM, revealing a significant difference between SIM and GIM (P < 0.0005). For each microsatellite marker analysed, there were obvious differences in frequency among the three conditions. Das-1 reactivity was significantly higher in SIM than in CIM or GIM (P < 0.0001, both). Interestingly, both genetic instability and Das-1 reactivity in SIM showed a significantly higher incidence in patients with H. pylori infection than in those without (P < 0.005 and P < 0.01, respectively)., Conclusions: SIM is distinct from CIM and GIM, and the pathogenesis of SIM, like that of GIM, is associated to some degree with H. pylori infection in a Japanese population.

In 2007 eight epidemic clusters (more than 15 cases in each) and other sporadic cases of measles occurred in Hokkaido district, Japan. A total of 850 cases were identified. Approximately half of them were > or = 15 years of age, resulting in a huge public health problem in the community associated with school closings, and 31% of the cases reported that they already had a history of vaccination. Of 28 isolates of the measles virus detected, all were identified as genotype D5, identical to the type isolated in other areas of Japan, suggesting that a highly homologous measles virus circulated in Japan. The occurrence pattern of measles patients and molecular epidemiology indicated that the measles virus that spread in Hokkaido district might not be indigenous.

Genetic or epigenetic alterations in Barrett's esophagus (BE) with/without Helicobacter pylori (H. pylori) infection remain unclear. We examined the effects of H. pylori infection on genetic instability (GIN), the CpG island methylation status and a biomarker related to BE carcinogenesis. We analyzed 113 Japanese individuals with endoscopically suspected BE. The patients included, Group CLE (n = 25): no specialized intestinal metaplasia (SIM) in a columnar lined epithelium (control); Group BE (n = 88): all had SIM. Microsatellite instability and a loss of heterozygosity as GIN, the methylation status at hMLH1, E-cadherin, p16 and APC, and immunoreactivity using a monoclonal antibody (mAb) Das-1, which specifically reacts with BE, were evaluated. Nine additional patients with BE were prospectively followed up for 2 years after successful H. pylori eradication. The frequency of GIN, methylation at E-cadherin and APC, and mAb Das-1 reactivity in Group BE was significantly higher than that in Group CLE (p < 0.0001, p < 0.0001 and p < 0.005, and p < 0.0001, respectively). Furthermore, GIN, E-cadherin methylation and mAb Das-1 reactivity showed a significantly higher incidence in patients with H.pylori infection than in those without H. pylori infection (p < 0.01, p < 0.005, and p < 0.01, respectively). Interestingly, the patients from Group BE were observed to change to a stable state of molecular alterations in 60% for GIN, 42.9% for E-cadherin methylation and 55.6% for APC methylation, or a reduction of mAb Das-1 reactivity was noted in 25% following eradication. H. pylori infection may therefore affect these molecular alterations associated with the pathogenesis of BE, to some degree, in the Japanese population.

Trichophyton tonsurans has been reported to be the causative agent of an epidemic of tinea corporis and tinea capitis among Japanese judoists and wrestlers. A molecular method using restriction enzyme analysis of PCR-amplified fragments targeting the non-transcribed spacer (NTS) region of ribosomal RNA genes in fungal nuclei was applied to a total of 232 strains of T. tonsurans isolated in Japan. Six molecular types, i.e., NTS types I, II, III, IV, V, and VI, were clearly detected in restriction analysis of fragments digested with MvaI and AvaI together. Of the 232 strains, 199 were classified as NTS I, 21 as NTS II, 7 as NTS III, 3 as NTS IV, 1 as type V, and 1 as type VI. Whereas the NTS I strains were found nationwide, most of the NTS II and NTS III strains were limited to central Japan. Of 164 strains isolated from judoists, 160 were classified as NTS I, which suggests that the majority of the cases were caused by a clonal lineage. On the other hand, the 48 strains isolated from wrestlers showed more variety, with 27 strains classified as NTS I, 17 as NTS II, and 4 as NTS III. We concluded that the epidemic was caused by at least three lineages of T. tonsurans. NTS VI strains, the major molecular type among sporadically isolated strains, were not observed among the epidemic strains, and strains of this type did not contribute to the present epidemic.

Objective: To estimate the rate that subjects with Mild Memory Impairment /Not Dementia (MMI/ND) shifted to dementia in a population-based cohort and to establish simple diagnostic methods for identification of high-risk persons for dementia., Methods: Subjects in a community-based elderly cohort of MMI/ND were followed longitudinally. Subjects were selected from the participants in the first Nakayama study. MMI/ND was defined as memory deficit with objective memory assessment, without dementia, impairment of general cognitive function, or disability in activities of daily living. The conversion rate was calculated using the person-year method., Results: At baseline, the sample consisted of 104 subjects (59 female; 45 male) selected from 1,162 community dwellers aged over 65 year. During the five-year follow-up, 14 subjects died, 13 moved to other communities, and six refused to participate further. Eleven (10.6%) subjects were diagnosed with Alzheimer's disease (AD), five (4.8%) were diagnosed with vascular dementia (VaD), and six (5.8%) were diagnosed with dementia of other etiology. The annual conversion rate that MMI/ND shifted to AD is calculated on 8.5% per 100 person-year, and shifted to dementia on 16.1% per 100 person-year in this survey., Conclusions: The rate at which subjects with MMI/ND whose conditions shifted to dementia was the same as the rate that subjects with mild cognitive impairment (MCI) shifted to dementia in a previous report. It would be useful to identify groups of high-risk individuals for dementia by simple diagnostic methods., (Copyright (c) 2006 John Wiley & Sons, Ltd.)

At the 48th Annual Meeting of The Society for Japanese Medical Mycology, held in October, 2004, we reported our findings from a survey on Trichophyton tonsurans infections in the Hokuriku and Kinki regions of Japan. The survey revealed that a few epidemics had occurred across these regions. In this article, we introduce our subsequent studies relating to 1) molecular epidemiology of isolates taken from people in many parts of Japan and 2) factors affecting adequate sampling of the scalp with hairbrushes, essential for surveying and monitoring the infection. In total, 198 isolates of Trichophyton tonsurans were analyzed using restriction fragment length polymorphisms of the non-transcribed spacer regions of ribosomal RNA genes. The restriction enzyme Mva I indicated two molecular types of strains, implying that the causative agents of the epidemic had different origins. None of the isolates obtained from the epidemic showed the same restriction profile as that of isolates from aged and sporadic cases. The published hairbrush method suitable for obtaining samples from the scalp of Judo trainees was reevaluated by changing several factors. We found that sampling should not be done soon after the students' physical training because other fungal elements may give a false positive, samples should not be obtained from students who have recently applied topical antimycotics, and samples should be taken under the guidance of qualified instructors familiar with the sampling method.

In June 2004, information was gathered on Trichophyton tonsurans infections, both past and current, in the Hokuriku and Kinki regions of central-western Honshu island, Japan, by questionnaires sent to 185 dermatologists who were members of the local medical mycologist associations Hokuriku Shinkin Kondan-kai and Kansai Shinkin Kondan-kai. Of the 111 (59.4%) who returned the completed questionnaire, 32 (28.8%) had seen patients infected with T. tonsurans including suspicious cases. The earliest recorded cases were linked to an endemic that occurred in 1994 or 1995 among a high school wrestling team in Toyama. The majority of the dermatologists saw their first case between 2001 and 2003. When the patients were grouped according to contact sports, judo players formed the largest group, followed by wrestlers. When grouped according to age, high school students formed the largest group, but the endemic had also expanded among junior high school students and adults, and there was one nursery school child who was a member of a judo club. Seventy-four of the dermatologists were sent sterilized hairbrushes to collect samples from patients suspected as having tinea capitis during July and September 2004. Trichophyton tonsurans was detected in samples from 6 patients. To investigate the molecular epidemiology, 71 of the clinical strains of T. tonsurans isolated from the Hokuriku and Kinki regions were analyzed using restriction fragment length polymorphisms of the non-transcribed spacer regions of ribosomal RNA genes. With the restriction enzyme Mva I, two molecular types were detected among the strains, indicating that the causative agents of the endemic were derived from different origins.

Objective: To determine the prevalence of mental and behavioural disturbances associated with dementia in elderly people living in the Japanese community of Nakayama., Methods: A door to door three phase population survey was carried out on all persons aged 65 years and older living at home. The study included a psychiatric interview, neurological and neuropsychological examination, and cranial computed tomography. Participants with dementia were rated on the neuropsychiatric inventory., Results: Of 1438 inhabitants, 1162 (81.0%) completed the protocol. The prevalence of dementia was 4.8%. Of the 60 participants with dementia (Alzheimer's disease 35%, vascular dementia 47%, and dementia from other causes 17%), 53 (88.3%) had shown one or more mental and behavioural disturbances. Apathy/indifference (56.7%), followed by agitation/aggression (35%), aberrant motor behaviour (31.7%), and irritability (31.7%) were the common symptoms. More productive (positive) symptoms such as delusions and aberrant motor behaviour were found in the Alzheimer group than in the vascular dementia group., Conclusions: A wide range of dementia associated mental and behavioural disturbances developed in the majority of community dwelling individuals with dementia. The findings suggest that a screening programme focusing on identifying these symptoms should be included in the physician's diagnostic tools for dementia.