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Objectives: Patients with myeloproliferative neoplasms (MPNs) are at higher risk of developing secondary malignancies. In this study, we focused on patients with MPNs that complicated lymphoid neoplasms. To analyze the real-world status of lymphoid neoplasm treatment in patients with pre-existing MPNs in Japan, we conducted a multicenter retrospective study., Methods: Questionnaires were sent to collect the data on patients who were first diagnosed with either polycythemia vera, essential thrombocythemia or myelofibrosis and who later were complicated with lymphoid neoplasms defined as malignant lymphoma, multiple myeloma, or chronic lymphocytic leukemia/small cell lymphoma., Results: Twenty-four patients with MPNs complicated by lymphoid neoplasms were enrolled (polycythemia vera, n  = 8; essential thrombocythemia, n  = 14; and primary myelofibrosis, n  = 2). Among these, diffuse large B-cell lymphoma (DLBCL) was the most frequently observed ( n  = 13, 54.1%). Twelve (92.3%) of the patients with DLBCL received conventional chemotherapy. Among these 12 patients, regarding cytoreductive therapy for MPNs, 8 patients stopped treatment, one continued treatment, and two received a reduced dose. Consequently, most patients were able to receive conventional chemotherapy for DLBCL with a slightly higher dose of granulocyte colony-stimulating factor support than usual without worse outcomes. All 3 patients with multiple myeloma received a standard dose of chemotherapy., Conclusion: Our data indicate that if aggressive lymphoid neoplasms develop during the course of treatment in patients with MPNs, it is acceptable to prioritize chemotherapy for lymphoma.

Understanding the genetic mechanisms that underlie innate fear behavior is essential for improving the management and performance of the poultry industry. This study aimed to map QTL associated with innate fear responses in open field (OF) and tonic immobility (TI) tests, using an F2 chicken intercross population between 2 behaviorally distinct breeds: the aggressive Japanese Oh-Shamo (OSM) and the docile White Leghorn T-line (WL-T). Genome-wide QTL analysis for the OF and TI traits was conducted using 2,109 single nucleotide polymorphism (SNP) markers obtained through restriction site-associated DNA sequencing (RAD-seq). While several suggestive QTL were identified for TI and OF traits at genome-wide 20% significance threshold levels, the analysis revealed 2 significant QTL for 2 OF traits (total distance and maximum speed) at genome-wide 5% significance threshold levels. These significant QTL were located between 12.34 and 30.49 megabase (Mb) on chromosome 1 and between 40.02 and 63.38 Mb on chromosome 2, explaining 6.75 to 7.40% of the total variances. These findings provide valuable insights for the poultry industry, particularly in refining chicken management strategies and informing targeted breeding efforts., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Since MPL mutation is a rare driver gene mutation found in a small number of essential thrombocythemia (ET) patients, the clinical characteristics of patients with MPL mutations and their association with thrombotic events have not yet been elucidated in Japan., Methods: We enrolled 579 Japanese ET patients based on the diagnostic criteria of the WHO classification 2017 and compared clinical characteristics of MPL -mutated patients ( n  = 22; 3.8%) to JAK2 V617F-mutated ( n  = 299; 51.6%), CALR -mutated ( n  = 144; 24.9%), and triple-negative (TN) ( n  = 114; 19.7%) patients., Results: Thrombosis during follow up was observed in 4 out of 22 (18.2%) in the MPL -mutated group, which was the highest among all driver gene mutation groups ( JAK2 V617F-mutated, 8.7%; CALR -mutated, 3.5%; TN,1.8%). The MPL- and JAK2 V617F-mutated groups had worse thrombosis-free survival (TFS) than the CALR -mutated ( p  = 0.043) and TN groups ( p  = 0.006). Univariable analysis revealed that a history of thrombosis was a possible risk factor for thrombosis among MPL -mutated patients (hazard ratio: 9.572, p  = 0.032)., Conclusions: MPL -mutated ET patients should require more intensive management to prevent recurrence of thrombosis.

Objective: Current guidelines for essential thrombocythemia (ET) patients recommend different treatment approaches based on thrombosis risk stratification models. However, these recommendations may not be applicable to some patients under real clinical settings. Therefore, we carried out a retrospective real-world validation study., Methods: Thrombosis-free survival (TFS) was compared between treatment naïve ET patients receiving different treatment approaches. ET patients were stratified by three representative risk models, the conventional, the International Prognostic Score for thrombosis in ET (IPSET-thrombosis), and revised IPSET-thrombosis. Treatment decisions were largely made by individual physicians, taking into account patient preferences and backgrounds., Results: A total of 179 ET patients were included, and thrombotic events were observed in 26 patients. TFS was significantly longer in high-risk patients of all risk models receiving a combination of cytoreductive therapy (CRT) and antiplatelet therapy (APT) compared to CRT alone. Similar results were seen in intermediate-risk patients stratified by IPSET-thrombosis. In contrast, in very low- and low-risk patients of all risk models, TFS was not affected by addition of CRT, indicating that observation or APT alone is an appropriate treatment approach for these patients., Conclusion: We demonstrate that current guidelines provide optimal treatment approaches for Japanese ET patients under real-world clinical settings.

Background: Two previous phase 3, double-blind, randomized, placebo-controlled trials showed that duloxetine 60 mg/day for 14 weeks significantly improved pain and quality of life in Japanese patients with knee osteoarthritis or chronic low back pain. In their open-label extension studies, these improvements were maintained for ≥48 weeks. This post-hoc analysis assessed the relationship between initial response to duloxetine and long-term pain reduction and quality of life in patients with knee osteoarthritis or chronic low back pain., Methods: Patients (knee osteoarthritis: N = 43; chronic low back pain: N = 41) were subdivided based on extent of pain reduction from baseline to Week 4 of duloxetine (≥30%, 10-30%, or <10% reduction in Brief Pain Inventory-Severity average pain score). Outcome measures were changes from baseline for Brief Pain Inventory-Severity and Brief Pain Inventory-Interference at regular intervals up to Week 65., Results: Mean change from baseline in Brief Pain Inventory-Severity was greater in patients with ≥30% early pain reduction than in patients with <10% early pain reduction through Week 27 for both conditions, and also Weeks 47-65 for back pain. Compared with the <10% early pain reduction group, mean change from baseline in the average of seven Brief Pain Inventory-Interference domain scores was greater in the ≥30% or 10-30% early pain reduction groups for knee osteoarthritis (except Weeks 63-65), and in the ≥30% early pain reduction group for chronic low back pain through Week 19., Conclusions: These results suggest that patients with knee osteoarthritis who respond well to duloxetine in the first month might experience sustained, long-term pain relief with generally greater quality-of-life improvement than patients with poor initial response. Patients with chronic low back pain who had strong initial response may experience a greater long-term pain relief, but not greater quality-of-life improvement, than patients with poor initial response., Competing Interests: Declaration of competing interest NI, TT, MI, and TO are full-time employees of and minor stockholders in Shionogi & Co., Ltd. TT is also a stockholder in Takeda Pharmaceutical Company Limited. YU has received grants to his institution from the Japan Society for the Promotion of Science (this study); consulting fees or honoraria and travel support from Shionogi & Co., Ltd. (this study) and Eli Lilly Japan K.K. (this study); consultancy fees from Japan Tissue Engineering Co., Ltd; and payment for lectures from Japan Tissue Engineering Co., Ltd., Chugai Pharmaceutical Co., Ltd, Shionogi & Co., Ltd., Kaken Pharmaceutical Co., Ltd, and Teijin Pharma Limited. SK has received payment for expert testimony from Nippon Shinyaku Co., Ltd., Shionogi & Co., Ltd., Pfizer Japan Inc., Asahi Kasei Pharma Corporation, Eli Lilly Japan K.K., and Hisamitsu Pharmaceutical Co., Inc.; payment for lectures from Daiichi Sankyo Co., Ltd., Shionogi & Co., Ltd., Eli Lilly Japan K.K., Pfizer Japan Inc., Hisamitsu Pharmaceutical Co., Inc., Chugai Pharmaceutical Co., Ltd., Kaken Pharmaceutical Co., Ltd., Eisai Co., Ltd., Astellas Pharma Inc., AbbVie GK, Taisho Pharma Co., Ltd., Asahi Kasei Pharma Corporation, HOYA Technosurgical Corporation, and Nippon Zoki Pharmaceutical Co., Ltd; and payment for manuscript preparation from NHK Educational Corporation., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: It is estimated that approximately 50% of patients with hepatitis C virus (HCV) infection in Japan are currently over 75 years old. However, patients aged ≥ 75 years are typically underrepresented in clinical trials of direct-acting antivirals. This study aimed to evaluate the efficacy and safety of glecaprevir and pibrentasvir (G/P) treatment in Japanese patients with HCV infection aged ≥ 75 years., Methods: This multicenter, retrospective study included 271 Japanese patients with HCV infection from 12 centers in Miyazaki Prefecture, Japan. Demographic, clinical, virological, and adverse events (AEs) data obtained during and after G/P treatment were collected from medical records. The patients were divided into two groups: younger (n = 199, aged < 75 years) and older (n = 72, aged ≥ 75 years). Virological data and AEs were analyzed according to the age group., Results: In intention-to-treat (ITT) and per-protocol analyses, the overall sustained virological response 12 (SVR12) rates were 93% and 98.8%, respectively. Two patients in the older group and 14 patients in the younger group dropped out before SVR12 assessment. Although patients in the older group tended to have liver cirrhosis, 95.8% in the older group and 92% in the younger group achieved SVR12 in the ITT analysis (P = 0.404). In total, 48 (17.7%) patients experienced treatment-related AEs. Common AEs during treatment included pruritus, headache, and fatigue. The AEs were not significantly different between the two groups., Conclusions: Compared with younger patients, older patients showed similar virological response and tolerance to G/P treatment., (© 2022. The Author(s).)

Objective: The goal of this study was to evaluate the efficacy and safety of duloxetine in children and adolescents (9-17 years of age) with major depressive disorder (MDD) in Japan. Methods: This study consists of two clinical trials. First, a 6-week, randomized double-blind placebo-controlled clinical trial (RCT) was conducted. The primary endpoint of RCT was the change in Children's Depression Rating Scale-Revised (CDRS-R) total scores from baseline. Following RCT, an open-label long-term extension trial (OLE) was conducted to investigate the longer-term safety of duloxetine for ∼1 year. Results: In RCT, CDRS-R total score changes from baseline to 6 weeks after the start of administration (primary endpoint) were -21.03 in the duloxetine group ( n  = 74) and -22.42 in the placebo group ( n  = 74). No significant difference was observed in the primary endpoint between the groups ( p  = 0.5587). In addition, no significant difference was observed in secondary endpoints such as CDRS-R response rates. The proportion of patients with ≥1 treatment-emergent adverse event (TEAE) in RCT was significantly higher in the duloxetine group (78.7%) than in the placebo group (62.2%), and most were mild or moderate in severity. Changes in CDRS-R total scores during OLE, in consecutive patients from the duloxetine group in RCT ( n  = 63), or placebo group ( n  = 59) in RCT, and newly enrolled patients ( n  = 28), were -12.1, -11.3, and -17.8, respectively. The proportion of patients with ≥1 TEAE in OLE was 90.5%, 88.1%, and 89.3% in the respective groups, and most of them were mild or moderate in severity. Conclusions: Duloxetine did not show superiority to placebo in efficacy in children and adolescents with MDD in Japan. Overall reported TEAEs were consistent with the currently available duloxetine safety profile and no new safety finding was observed in the two clinical trials.

Background/aim: Direct-acting antiviral (DAA) therapies for patients with hepatitis C virus (HCV) infection deliver higher cure rates and lower frequencies of adverse events than existing therapies, though DAA treatment costs $45,000-64,000 in Japan. The prognosis of patients who require new long-term care insurance (LTCI) certification is inferior to that of patients who do not. Here, we clarify the factors associated with new LTCI certification in elderly patients with HCV infection who undergo DAA therapy., Patients and Methods: We retrospectively surveyed 53 patients aged ≥70 years who were treated with DAAs, and evaluated the factors associated with new LTCI certification., Results: Of 53 patients, 10 required new LTCI certification. Age ≥85 years and a modified Japanese Cardiovascular Health Study index ≥2 were independently associated with new LTCI certification., Conclusion: In elderly HCV patients, poor frailty status strongly predicted new LTCI certification after DAA therapy., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Patients with primary myelofibrosis (PMF) have a poorer prognosis than those with other subtypes of myeloproliferative neoplasms (MPNs). To investigate the relationship between gene mutations and the prognosis of Japanese PMF patients, we analyzed mutations in 72 regions located in 14 MPN-relevant genes (CSF3R, MPL, JAK2, CALR, DNMT3A, TET2, EZH2, ASXL1, IDH1/2, SRSF2, SF3B1, U2AF1, and TP53) utilizing a target resequencing platform. In our cohort, ASXL1 mutations were more frequently detected in both overt and prefibrotic PMF patients than other mutations. The frequency of ASXL1 mutations was slightly higher among overt PMF patients than among prefibrotic PMF patients (44.6% vs 25.0%, FDR = 0.472). Decision tree classification algorithms revealed that ASXL1, EZH2, and SRSF2 mutations were associated with a poor prognosis for overt PMF. Overall survival was significantly shorter in patients harboring ASXL1, EZH2, or SRSF2 mutations than in those without these mutations (p = 0.03). These results suggest that, as reported in Western countries, MIPSS70 is applicable to Japanese PMF patients and ASXL1, EZH2, and SRSF2 mutations may be utilized as surrogate markers of a poor prognosis.

Background: Central sensitization, including dysfunction of descending inhibitory pain pathways, may contribute to multisite pain in patients with chronic musculoskeletal conditions. Duloxetine is a centrally acting analgesic that effectively reduces pain in patients with knee osteoarthritis. Here we assessed the efficacy of duloxetine (60 mg/day) in Japanese patients (N = 353) with pain due to knee osteoarthritis based on the number of painful body sites, determined using the Michigan Body Map., Methods: Post hoc analysis of a phase 3, randomized, placebo-controlled trial (ClinicalTrials.gov; NCT02248480)., Results: At Week 14, the change from baseline in Brief Pain Inventory-Severity average pain score ("pain reduction") was significantly greater with duloxetine compared with placebo in patients with 3, 4, or ≥5 painful sites, but not in patients with 1 or 2 painful sites. In patients with ≥3 painful sites (57% of patients), pain reduction was significantly greater with duloxetine (n = 100) compared with placebo (n = 101) throughout the study (least squares mean change from baseline to Week 14: -2.68 vs -1.68). Greater pain reduction with duloxetine (n = 77) than placebo (n = 75) also occurred in patients with ≤2 painful sites, although the between-group difference was significant only at Week 4., Conclusions: These results are consistent with duloxetine enhancing the activity of descending inhibitory pain pathways that are dysfunctional in patients with central sensitization and multisite pain. In addition, these results suggest that duloxetine may be an effective choice of analgesic for patients with knee osteoarthritis and multisite pain., Competing Interests: Declaration of Competing Interest NI, TT, MI, and TO are full-time employees and minor stockholders in Shionogi & Co., Ltd. TT is also a stockholder in Takeda Pharmaceutical Company Limited. YU has received honoraria/consulting fees, travel support, fees for participation in review activities, fees for writing assistance, medicine, equipment, and administrative support, and/or grants from Shionogi & Co., Ltd. (this study); Eli Lilly Japan K.K. (this study); Astellas Pharma Inc.; Asahi Kasei Pharma Corporation; Chugai Pharmaceutical Co., Ltd.; Daiichi Sankyo Co., Ltd.; Kaken Pharmaceutical Co., Ltd.; Nippon Zoki Pharmaceutical Co., Ltd.; Seikagaku Corporation; Taisho Toyama Pharmaceutical Co., Ltd; Teijin Pharma Limited; Pfizer Japan Inc.; Japan Tissue Engineering Co., Ltd.; Ayumi Pharmaceutical Corporation; Hisamitsu Pharmaceutical Co., Inc.; Eisai Co., Ltd.; Meira Co.; Stryker Japan K.K.; and Takeda Pharmaceutical Company Limited. SK has received grants, honoraria, reviewing fees, payment for lectures, fees for writing assistance, medicines, equipment, and/or administrative support from Shionogi & Co., Ltd. (this study); Eli Lilly Japan K.K. (this study); Asahi Kasei Pharma Corporation; Eisai Co., Ltd.; Ono Pharmaceutical Co., Ltd.; Kaken Pharmaceutical Co., Ltd.; Johnson & Johnson K.K.; Daiichi Sankyo Co., Ltd.; Taisho Toyama Pharmaceutical Co., Ltd.; Takeda Pharmaceutical Company Limited; Nippon Zoki Pharmaceutical Co., Ltd.; Hisamitsu Pharmaceutical Co., Inc.; Pfizer Japan Inc.; Janssen Pharmaceutical K.K.; Ayumi Pharmaceutical Corporation; Taiho Pharmaceutical Co., Ltd.; Chugai Pharmaceutical Co., Ltd.; Teijin Pharma Limited; Astellas Pharma Inc.; Nippon Shinyaku Co., Ltd.; Stryker Japan K.K.; Tsumura & Co.; and Otsuka Pharmaceutical Co., Ltd., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Steelmaking slags are a promising resource as artificial seaweed beds for the reconstitution of marine environments. To grow seaweed well, the formation of biofilms is an essential process in biofouling. This study focused on the formation of initial biofilms on steelmaking slag samples and analyzed the resulting bacterial communities using the next-generation sequencing technique. Three types of steelmaking slag were submerged in an area of Ise Bay in Mie Prefecture, Japan, for 3 and 7 days in the summer and winter seasons to allow the formation of biofilms. The bacterial communities of these biofilms were richer in sulfur-oxidizing bacteria compared to the biofilms formed on polyurethane sponges. It was found that Helicobacteraceae dominantly grew on the biofilms formed on the slag samples. This shows that steelmaking slags have potential to be used as artificial seaweed beds and marine water purifiers.

We retrospectively examined 106 cases of tapentadol use in Japan in August 2014 for cancer pain at our hospital.The advantage of the opioid medication tapentadol is that its introduction is suitable in patients undergoing anti-cancer treatment because of the low incidence of gastrointestinal symptoms, with glucuronidation involved in the metabolism, and lack of interactions with other drugs.However, depending on the dosage form and presence of swallowing disorders, the administration should be considered carefully.

Transcatheter aortic valve implantation (TAVI) is a viable treatment option for high-risk patients with severe aortic stenosis. In Japan, TAVI can be performed using first-generation self-expandable Medtronic CoreValve or balloon-expandable Edwards SAPIEN-XT from 2012. Since the durability and hemodynamic outcomes after transcatheter heart valve (THV) implantation in Japanese patients have not been clearly elucidated, we assessed serial changes in post-TAVI THV performances over a-3-year period by transthoracic echocardiography (TTE). From January 2012 to September 2014, among 83 patients with severe aortic stenosis, 26 underwent TAVI with CoreValve and 57 underwent TAVI with SAPIEN-XT. We assessed the serial changes in first post-implant (FPI) and 3-year post procedure THV hemodynamics by TTE. Valve performance was evaluated by serial assessment of aortic valve mean pressure gradient (PG) and aortic valve area (AVA) assessments. Three-year clinical outcomes were compared between the patients with CoreValve and those with SAPIEN-XT. Seventeen patients with CoreValve and 34 patients with SAPIEN-XT had FPI and 3-year TTEs. The AVA decreased significantly from FPI to 3-year follow-up among patients with SAPIEN-XT, but not among patients with CoreValve. The mean aortic PG decreased significantly from FPI to the 3-year follow-up point among patients with CoreValve; however, it was not significantly different from those with SAPIEN-XT. The absolute change in mean PG from FPI to the 3-year follow-up point decreased significantly among those with CoreValve compared to those with SAPIEN-XT. Clinical outcomes after TAVI were similar for both devices at 3-years after TAVI. In this study, long-term clinical outcomes for CoreValve and SAPIEN XT were similar. The 3-year THV performance of both devices was maintained after TAVI. Serial change in mean aortic PGs for CoreValve decreases significantly from FPI to the 3-year follow-up point compared to that for SAPIEN-XT.

Objective: To evaluate the safety and efficacy of duloxetine treatment for 52 weeks., Design: Multicenter, open-label, phase III clinical study., Setting: Forty-one medical institutions in Japan., Subjects: Japanese patients with chronic low back pain (CLBP)., Methods: Duloxetine 60 mg once-daily was administered for 52 weeks. Safety was evaluated based on adverse events (AEs), vital signs, laboratory test values, electrocardiogram, Columbia-Suicide Severity Rating Scale, and occurrence of falls. The efficacy outcome measures were the Brief Pain Inventory (BPI; average pain, worst pain, least pain, and pain right now), BPI Interference, Patient's Global Impression of Improvement (PGI-I), Clinical Global Impressions of Severity (CGI-S), Roland-Morris Disability Questionnaire-24 (RDQ-24), 36-Item Short-Form Health Survey (SF-36), and European Quality of Life-5 Dimensions Questionnaire (EQ-5D)., Results: In total, 151 patients (83 who completed a 14-week placebo-controlled superiority trial and 68 newly registered patients) were enrolled. The incidence rates of AEs and adverse drug reactions (ADRs) were 86.1% and 50.3%, respectively. ADRs with an incidence of ≥5% were somnolence, constipation, nausea, and dry mouth. Treatment discontinuation for AEs occurred in 16 patients. A significant reduction in the BPI average pain score (mean ± SD) was observed at all assessment time points from week 2 (-1.02 ± 1.37) to week 50 (-2.26 ± 1.63), compared with baseline. BPI pain severity (worst pain, least pain, and pain right now), BPI Interference, PGI-I, CGI-S, RDQ-24, SF-36, and EQ-5D showed significant improvement., Conclusion: Japanese patients with CLBP had significant pain reduction over 52 weeks without new safety concerns., (© 2019 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: This study investigated the relationship between the timing of ventricular tachycardia or ventricular fibrillation (VT or VF) and prognosis in patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI)., Background: It is unknown whether the timing of VT/VF occurrence affects the prognosis of patients with AMI., Methods: From January 2004 to December 2014, 1004 patients with AMI underwent primary PCI. Of these patients, 888 did not have VT/VF (non-VT/VF group) and 116 had sustained VT/VF during prehospitalization or hospitalization. Patients with VT/VF were divided into two groups: early VT/VF (VT/VF occurrence before and within 2 days of admission, 92 patients) and late VT/VF (VT/VF occurrence >2 days after admission; 24 patients) groups., Results: The frequency of VT/VF occurrence was high between the day of admission and the 2nd day and between days 6 and 10 of hospitalization. The late VT/VF group had a significantly longer onset-to-balloon time, lower ejection fraction, poorer renal function, and higher creatine phosphokinase (CK)-MB level on admission (p< 0.001). They also had a lower 30-day cardiac survival rate than the early VT/VF and non-VT/VF groups (42% vs. 76% vs. 96%, p < 0.001). Moreover, independent predictors of in-hospital cardiac mortality among patients with AMI who had sustained VT/VF were higher peak CK-MB [Odds ratio (OR: 1.001, 95%confidence interval (CI): 1.000-1.002, p= 0.03)], higher Killip class (OR: 1.484, 95%CI 1.017-2.165, p= 0.04), and late VT/VF (OR: 3.436, 95%CI 1.115-10.59, p= 0.03)., Conclusions: The timing of VT/VF occurrences had a bimodal peak. Although late VT/VF occurrence after primary PCI was less frequent than early VT/VF occurrence, patients with late VT/VF had a very poor prognosis., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2019 Takuma Takada et al.)

Background & Aims: Platelet transfusion is used to prevent hemorrhagic events in patients with thrombocytopenia undergoing invasive procedures, but there are many disadvantages. We evaluated the efficacy and safety of lusutrombopag in patients with chronic liver disease and thrombocytopenia undergoing invasive procedures., Methods: We performed a double-blind, parallel-group, phase 3 study of 96 patients with chronic liver disease and thrombocytopenia (platelet counts below 50,000/μL) undergoing invasive procedures from October 2013 to May 2014 at 81 centers in Japan. Patients were randomly assigned (1:1) to groups given once-daily lusutrombopag (3 mg) or placebo for up to 7 days. The primary efficacy endpoint was the proportion of patients not requiring platelet transfusion before the invasive procedure. The protocol-defined response (platelet count 50,000/μL or more with an increase of 20,000/μL or more from baseline) and the time course of the change in platelet count were also evaluated. Adverse events were recorded., Results: The proportions of patients who did not require preoperative platelet transfusion were 79.2% (38/48) in the lusutrombopag group and 12.5% (6/48) in the placebo group (P < .0001). A response was observed in 77.1% (37/48) of patients in the lusutrombopag group and 6.3% (3/48) of patients in the placebo group (P < .0001). In the lusutrombopag group without platelet transfusion, the median platelet count was 50,000/μL or more after 5 days; the mean time to reach the maximum platelet count was 13.4 days; and the number of days (adjusted mean) during which the platelet count was 50,000/μL or more was 21.09 days. Adverse drug reactions were reported in 8.3% of patients in the lusutrombopag group and 2.1% of patients in the placebo group. Two patients (1 per group) had a thrombotic event, but neither were associated with an excessive increase in platelet count (200,000/μL or more)., Conclusion: In a placebo-controlled trial, lusutrombopag was effective in achieving and maintaining the target platelet count in patients with chronic liver disease and thrombocytopenia undergoing invasive procedures. No significant safety concerns were raised. Japanese clinical trial registration no: JapicCTI-132323., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to clarify by histopathological examination the origin of oral membranous substances deposited on the palate, tongue, buccal mucosa and teeth., Background: Several investigators have reported membranous substances deposited in the mouths of bedridden elderly persons requiring nursing care without oral intake. However, the precise nature and origin of the substances are poorly understood., Methods: Sixty-nine specimens were taken from the oral cavity of bedridden patients, that is, the palate, dorsum of the tongue, the cheek and teeth. Sections were stained with haematoxylin and eosin stain, alcian-blue and periodic acid-Schiff stain (AB-PAS) and antibodies for pankeratin (AE1AE3) and leukocyte common antigen (LCA)., Results: All specimens showed a film-like nature coloured from tan to white, accompanied by a mucous substance. Histologically, specimens of all sites had a similar feature of the combination of basophilic amorphous and eosinophilic lamellar features. The basophilic substance was positive for AB-PAS, and PAS-positive glycogen granules were also noted in the lamellar structure. Immunochemistry revealed various degrees of pankeratin positive substance and LCA-positive inflammatory cell infiltration., Conclusion: The oral membranous substance was composed of keratin and mucin with inflammation. These results suggest that the deposition of the oral membranous substance is a pathological condition or oral mucositis caused by dry mouth., (© 2018 Gerodontology Association and John Wiley & Sons Ltd.)

Background: Thrombocytopenia represents an obstacle for invasive procedures in chronic liver disease (CLD) patients. We aimed to estimate the appropriate dose and evaluate the efficacy and safety of lusutrombopag for the treatment of thrombocytopenia before percutaneous liver radiofrequency ablation (RFA) for primary hepatic cancer in patients with CLD., Methods: In this multicenter, randomized, double-blind, placebo-controlled study conducted in Japan, 61 CLD patients with platelet count < 50 × 10 3 /µL at screening were randomized to placebo or lusutrombopag 2, 3, or 4 mg once daily for 7 days, followed by a 28-day post-treatment assessment period. The primary efficacy endpoint was the proportion of patients who did not require platelet transfusion before RFA. The pre-specified key secondary efficacy endpoint was the proportion of responders. Adverse events (AEs) and thrombosis-related AEs were evaluated., Results: The proportion of patients who did not require platelet transfusion before RFA and that of responders were significantly higher (p < 0.01) in the 2-mg (80.0, 66.7%), 3-mg (81.3, 68.8%), and 4-mg groups (93.3, 80.0%) compared with the placebo group (20.0, 6.7%) and showed a dose-dependent effect. The incidence of AEs was 97.8 and 100% in the lusutrombopag (all groups) and placebo groups, respectively; no dose-related increase was observed. Four patients experienced thrombosis-related events (one each in the placebo and 2-mg groups, and two in the 4-mg group). A total of 16 (18%) adverse drug reactions occurred in the safety analysis set., Conclusions: Lusutrombopag 3 mg once daily for 7 days was effective without raising concerns about excessive increases in platelet count., Clinical Trial Registration: The study is registered at JapicCTI-121944.

Background: Congenital ichthyoses (CIs) adversely affect quality of life (QOL) in patients. However, the effects of CIs on patient QOL have not been studied sufficiently., Objective: To investigate the association between disease severity and QOL in patients with harlequin ichthyosis (HI) and ichthyosis: syndromic forms (ISFs) METHODS: Clinical information of patients with HI and ISFs from 2010 to 2015 were obtained from 100 dermatology departments/divisions of principal institutes/hospitals throughout Japan. We examined the relationship between disease severity and QOL in patients with HI and ISFs. Patients who were aged 8 years or older and participated in a multicenter retrospective questionnaire survey in Japan were assessed by dermatology life quality index (DLQI, range of 0-30) and clinical ichthyosis score (range of 0-100)., Results: Netherton syndrome patients had a significantly higher risk of allergy to food or environmental allergens than patients with other phenotypes. Keratitis-ichthyosis-deafness (KID) syndrome patients showed a significantly higher risk of skin infections than patients with other phenotypes. Complete data on DLQI were obtained from 13 patients, whose median age was 21 (8-71) years. Nine patients were male, and 4 were female. Systemic retinoids were administrated to 2 of the 3 HI patients. The Spearman's correlation coefficient between the clinical ichthyosis score and DLQI was 0.611 (P < 0.05)., Conclusion: We confirmed that Netherton syndrome and KID syndrome patients have a higher risk of allergy to food or environmental allergens and of skin infections, respectively. QOL impairment correlates with disease severity in HI and ISFs patients., (Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Objectives: This study investigated the diagnostic performance of instantaneous wave-free ratio (iFR) in patients with aortic valve stenosis (AS)., Background: The iFR was introduced as a new, nonpharmacologic stress index of coronary stenosis severity. However, the diagnostic performance of iFR has not been sufficiently explored in patients with severe AS., Methods: We analyzed 95 consecutive patients with AS (57 women) demonstrating intermediate coronary artery stenosis (116 vessels), and compared the iFR values with fractional flow reserve (FFR) values and with adenosine-stress myocardial perfusion imaging as indicators of myocardial ischemia., Results: The median value and interquartile range (first quartile [Q1], third quartile [Q3]) of the iFR was 0.86 (Q1 to Q3 range, 0.76 to 0.93), and that of the FFR was 0.84 (Q1 to Q3 range, 0.76 to 0.91). The iFR values correlated well with the FFR values (R = 0.854; p < 0.0001). A receiver operating characteristic analysis demonstrated an optimal cutoff of 0.82 for the iFR to indicate an FFR ≤0.75, with an area under the curve of 0.92. The optimal iFR cutoff value indicating myocardial ischemia on perfusion scintigraphy was 0.82 (area under the curve: 0.84)., Conclusions: In patients with severe AS, a good correlation exists between iFR and FFR. Both the iFR and FFR values exhibit good correlation with perfusion scintigraphy-identified myocardial ischemia. The iFR could be a safe diagnostic tool for patients with severe AS. (The Impact of FFR and iFR in Patients with Severe Aortic Stenosis; UMIN000024479)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: The persistence of left ventricular (LV) hypertrophy is associated with poor clinical outcomes after transcatheter aortic valve implantation (TAVI) for aortic stenosis. However, the optimal medical therapy after TAVI remains unknown. We investigated the effect of renin-angiotensin system (RAS) blockade therapy on LV hypertrophy and mortality in patients undergoing TAVI., Methods: Between October 2013 and April 2016, 1215 patients undergoing TAVI were prospectively enrolled in the Optimized CathEter vAlvular iNtervention (OCEAN)-TAVI registry. This cohort was stratified according to the postoperative usage of RAS blockade therapy with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). Patients with at least two prescriptions dispensed 180 days apart after TAVI and at least a 6-month follow-up constituted the RAS blockade group (n=371), while those not prescribed any ACE inhibitors or ARBs after TAVI were included in the no RAS blockade group (n=189)., Results: At 6 months postoperatively, the RAS blockade group had significantly greater LV mass index regression than the no RAS blockade group (-9±24% vs -2±25%, p=0.024). Kaplan-Meier analysis revealed a significantly lower cumulative 2-year mortality in the RAS blockade than that in the no RAS blockade group (7.5% vs 12.5%; log-rank test, p=0.031). After adjusting for confounding factors, RAS blockade therapy was associated with significantly lower all-cause mortality (HR, 0.45; 95% CI 0.22 to 0.91; p=0.025)., Conclusions: Postoperative RAS blockade therapy is associated with greater LV mass index regression and reduced all-cause mortality. These data need to be confirmed by a prospective randomised controlled outcome trial., Competing Interests: Competing interests: Drs SS, MY, NT, TN, MA, SS, YW and KH are proctors for Edwards Lifesciences (transfemoral-TAVI with SAPIEN-XT valves)., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Fibromyalgia is characterized by widespread pain and is often accompanied by accessory symptoms. There are limited treatment options for this condition in Japan. Therefore, we conducted a phase III study to assess the efficacy and safety of duloxetine in Japanese patients with fibromyalgia., Methods: This randomized, double-blind, placebo-controlled, parallel-group trial was conducted in Japan. Outpatients who met the American College of Rheumatology 1990 criteria for fibromyalgia and whose Brief Pain Inventory (BPI) average pain score was ≥4 were randomized to duloxetine 60 mg or placebo once daily for 14 weeks. The primary efficacy measure was the change in the BPI average pain score from baseline. Secondary efficacy, quality of life (QoL), and safety outcomes were also evaluated. Mixed-effects model repeated-measures (MMRM) analysis and last observation carried forward (LOCF) analysis of covariance were used to evaluate the primary efficacy measure., Results: Overall, 393 patients were randomized to receive either duloxetine (n = 196) or placebo (n = 197). The MMRM analysis revealed no significant difference between duloxetine and placebo regarding the change in BPI average pain scores at week 14. Based on LOCF analysis, a statistically significant improvement in the change in BPI average pain scores at week 14 was observed for patients treated with duloxetine compared with placebo. Duloxetine treatment was associated with improved outcomes in nearly all secondary and post hoc analyses. The treatment was generally well tolerated. Somnolence, nausea, and constipation were the most common treatment-emergent adverse events in the duloxetine group. The discontinuation rates due to treatment-emergent adverse events were similar in both groups., Conclusions: Although the MMRM analysis did not demonstrate superiority of duloxetine over placebo, duloxetine treatment was associated with improved outcomes in secondary and post hoc analyses of the mean change in the BPI average pain score and most of the secondary outcomes, including analgesia and QoL. Duloxetine treatment was safe and well tolerated. These results suggest that duloxetine treatment could be associated with improvements in pain relief and QoL in Japanese patients with fibromyalgia., Trial Registration: ClinicalTrials.gov Identifier: NCT01552057 . Registered 9 March 2012.

We experienced two cases of acute hepatitis E in Miyazaki Prefecture in the same period. The patients were unknown to each other and did not have any clear causes or common risk factors of hepatitis E virus (HEV) infection. Nucleotide sequences of the HEV isolates revealed that the two isolates were closely related but with different HEV genotype 3 strains. The two cases appeared to be infected from unknown and different sources. Molecular phylogenetic analysis indicated that the strains were probably descendants of the strains which had been isolated from swine herd in Miyazaki Prefecture 12 years previously. This result indicates that the strains persisted in pig farms, in wild life, or in the natural environment in this region. The source should be identified, and efforts should be made to prevent of the spread of the infection. One of the cases had acute facial paralysis, which might be an extra-hepatic manifestation of HEV infection.

Objective: The criteria for endoscopic resection for early gastric cancer include absolute and expanded indications. Consensus already exists for the absolute indications. However, the suitability of the expanded indications must be validated by long-term outcome analyses since such lesions have only recently become resectable with the development of endoscopic submucosal dissection. The aim of this study is to clarify the suitability of the expanded indications for the treatment of early gastric cancer with endoscopic submucosal dissection., Materials and Methods: The medical records of 1161 patients with early gastric cancers (1332 lesions) treated by endoscopic submucosal dissection and meeting the criteria for absolute or expanded indications without additional treatment with gastrectomy were divided into absolute indication group or expanded indication group., Results: Complete resection rates were 96.4% and 93.4% in absolute and expanded indication groups, respectively, with no significant differences between the groups. Delayed bleeding rates were significantly higher in the expanded indication group, whereas all cases were successfully managed conservatively. The 5-year overall survival and recurrence-free rates were 93.7%/99.77% and 90.49%/98.90% in the absolute and the expanded indication groups, respectively, with no significant differences between the groups for either measure. Multivariate analyses revealed that affected horizontal margin and tumor location were independent predictive factors for recurrence., Conclusion: The expanded indication group showed excellent post-endoscopic submucosal dissection short-term and long-term outcomes compared with the absolute indications group, demonstrating that expanded indications are suitable for endoscopic submucosal dissection for early gastric cancer.

Aim: To analyze hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) using the tumor-node-metastasis (TNM) staging system., Methods: We retrospectively analyzed 372 patients with HCC who underwent hepatectomy between 1980 and 2009. We studied the outcomes of HCC patients with PVTT to evaluate the American Joint Committee on Cancer TNM staging system (7(th) edition) for stratifying and predicting the prognosis of a large cohort of HCC patients after hepatectomy in a single-center. Portal vein invasion (vp) 1 was defined as an invasion or tumor thrombus distal to the second branch of the portal vein, vp2 as an invasion or tumor thrombus in the second branch of the portal vein, vp3 as an invasion or tumor thrombus in the first branch of the portal vein, and vp4 as an invasion or tumor thrombus in the portal trunk or extending to a branch on the contralateral side., Results: The cumulative 5-year overall survival (5yrOS) and 5-year disease-free survival (5yrDFS) rates of the 372 patients were 58.3% and 31.3%, respectively. The 5yrDFS and 5yrOS of vp3-4 patients (n = 10) were 20.0%, and 30.0%, respectively, which was comparable with the corresponding survival rates of vp1-2 patients (P = 0.466 and 0.586, respectively). In the subgroup analysis of patients with macroscopic PVTT (vp2-4), the OS of the patients who underwent preoperative transarterial chemoembolization was comparable to that of patients who did not (P = 0.747). There was a significant difference in the DFS between patients with stage I HCC and those with stage II HCC (5yrDFS 39.2% vs 23.1%, P < 0.001); however, the DFS for stage II was similar to that for stage III (5yrDFS 23.1% vs 13.8%, P = 0.330). In the subgroup analysis of stage II-III HCC (n = 148), only alpha-fetoprotein (AFP) > 100 mg/dL was independently associated with DFS., Conclusion: Hepatectomy for vp3-4 HCC results in a survival rate similar to hepatectomy for vp1-2. AFP stratified the stage II-III HCC patients according to prognosis.

Background: It is recommended that not only door-to-balloon time but also prehospital delay for primary percutaneous coronary intervention (PCI) should be improved. We investigated the effect of prehospital transfer pathway on onset-to-balloon time and prognosis in patients with ST-segment elevation myocardial infarction (STEMI) in Japan., Methods and results: We analyzed data from 540 consecutive patients with primary PCI for STEMI. Patient clinical data and mortality were compared between patients who visited the family physician or non-PCI-capable hospitals and were then transferred to PCI-capable centers (indirect transfer patients), and those who directly visited PCI-capable centers (direct transfer patients). Onset-to-balloon time was longer in indirect transfer patients than in direct transfer patients (mean, 270 min; range, 180-480 min vs. 180 min, 120-240 min; P<0.001). In addition, patient prognosis was evaluated on Cox proportional regression analysis. Cardiac death and all-cause death were significantly higher in indirect transfer patients (odds ratios [OR], 2.17; 95% confidence intervals [95% CI]: 1.17-4.01, P=0.01; OR, 1.71; 95% CI: 1.09-2.68, P=0.02). These results were confirmed using propensity score matching for adjusted analyses., Conclusions: Patients with indirect transfer to regional emergency departments of PCI centers had longer onset-to-balloon time and worse prognosis than those with direct transfer.

Background: Drug-induced pemphigus (DIP) shows clinical, histopathological and immunological features of pemphigus. However, little is known about immunological profiles in DIP., Objectives: To characterize clinical and immunological profiles in patients with DIP., Methods: We studied 17 Japanese patients with DIP who were treated at Kurume University Hospital or who consulted from other hospitals between 1997 and 2012. Complicated diseases, clinical and histopathological manifestations, responsible drugs and findings in immunofluorescence, enzyme-linked immunosorbent assays (ELISAs), immunoblotting (IB) and prognosis were analysed., Results: Eight of the 17 patients with DIP showed pemphigus foliaceus-like appearance, three showed pemphigus herpetiformis-like appearance, and six showed atypical bullous lesions. Responsible drugs were thiol-containing drugs in 16 patients (bucillamine in nine cases, d-penicillamine in four cases, and cetapril, thiopronine and captopril in one patient each), and a nonthiol drug, sulfasalazine, in one patient. By ELISAs and/or IB analyses, nine patients reacted only with desmoglein 1 (Dsg1), four reacted with Dsg1 and Dsg3, and four showed no specific reactivity. By IB of normal human epidermal extracts, in addition to positive reactivity with Dsg1, four patients with no detectable malignancy showed paraneoplastic pemphigus-like reactivity with the 210-kDa envoplakin and the 190-kDa periplakin. Four cases showed anti-Dsg3 antibodies without mucosal lesions. While 11 cases recovered after discontinuation of the causative drugs, six patients had a very protracted or intractable disease course, and might develop true pemphigus., Conclusions: The present study indicated that the majority of the patients with DIP studied showed a pemphigus foliaceus-type phenotype with anti-Dsg1 autoantibodies, caused by thiol-containing drugs., (© 2014 British Association of Dermatologists.)

In atherosclerosis, carotid artery stenosis (CAS), renal artery stenosis (RAS), lower extremity peripheral arterial disease (PAD), and coronary artery disease (CAD) are common pathologic lesions; their interrelationship is, however, unclear. We studied concomitant multiple atherosclerotic lesions in patients with CAD to understand their prevalence and relations. A cross-sectional analysis was performed on data from consecutive patients who underwent nonemergent coronary angiography. Simultaneous carotid and renal artery Doppler studies and ankle-brachial systolic pressure measurements were reviewed to diagnose concomitant lesions and their severity. The study included 1,734 patients (aged 71 ± 9 years; 70% men), with prevalences of CAS, RAS, lower extremity PAD, and CAD of 6%, 7%, 13%, and 72%, respectively. In patients with CAD (n = 1,253), the prevalences of CAS, RAS, and lower extremity PAD were 7%, 9%, and 16%, respectively; 24% CAD patients had ≥1 additional atherosclerotic lesion. Significant interactions among the prevalences of these lesions were found. In addition, the extent of CAD and the prevalences of CAS, RAS, and lower extremity PAD were significantly correlated. Multivariate analysis supported these relationships. In conclusion, the prevalences of CAS, RAS, lower extremity PAD, and CAD were strongly interrelated in the study population; CAD severity was related to that of other atherosclerotic lesions. Additional systematic screening of other concomitant atherosclerotic lesions is recommended, especially in CAD patients having multivessel disease, left main disease, and/or already diagnosed with other concomitant atherosclerotic lesions., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Object: After untethering of spinal dysraphism, some patients present with neurological deterioration, defined as retethered cord syndrome. It is known that surgical untethering is an option for improving the symptoms of retethered cord syndrome. Previous reports have shown that postoperative improvement in retethered cord syndrome was noted in the majority of patients presenting with pain, and in more patients with motor weakness than in those with urological symptoms. The authors speculate that subjective symptoms may be detected while symptoms are still reversible. In contrast, changes in urological function are less easy to diagnose, and delays in treatment may be complicated by advanced symptoms. In this study, patients with retethered cord syndrome were evaluated to investigate the benefits of performing routine urodynamic study to detect detrusor overactivity, which is considered to be a subclinical change of urological function, and to investigate the efficacy of early untethering surgery on the symptoms of retethered cord syndrome., Methods: Surgical indications and outcomes of 78 untethering operations (20 for myelomeningocele, 58 for spinal lipoma) for retethered cord syndrome were examined. Diagnosis of retethered cord syndrome was defined by a multidisciplinary spina bifida team, and included routine urodynamic study., Results: Preoperative symptoms included urological symptoms (70%), lower-extremity symptoms (45%), and others. The most frequent urological symptom was detrusor overactivity detected by urodynamic study (88.7%). Urinary incontinence was only found in 9.4% of patients. Postoperatively, progressive motor weakness improved in all patients, and sensory symptoms improved in 94%. Urological symptoms improved in 80% of the patients with urinary incontinence and in 75% of the patients with detrusor overactivity. Postoperative urodynamic study showed a significant increase in bladder volume (p < 0.05). The most common complication was temporary lower leg paresthesia that recovered at follow-up. Aggravated dysuria was noted in 3 patients., Conclusions: Early untethering operations offer symptomatic relief to patients with retethered cord syndrome. Urodynamic study findings, especially detrusor overactivity, are considered to be the most significant indicators for early diagnosis of retethered cord syndrome.

Aim: To re-evaluate the recent clinicopathological features of remnant gastric cancer (RGC) and to develop desirable surveillance programs., Methods: Between 1997 and 2008, 1149 patients underwent gastrectomy for gastric cancer at the Department of Digestive Surgery, Kyoto Prefectural University of Medicine, Japan. Of these, 33 patients underwent gastrectomy with lymphadenectomy for RGC. Regarding the initial gastric disease, there were 19 patients with benign disease and 14 patients with gastric cancer. The hospital records of these patients were reviewed retrospectively., Results: Concerning the initial gastric disease, the RGC group following gastric cancer had a shorter interval [P < 0.05; gastric cancer vs benign disease: 12 (2-22) vs 30 (4-51) years] and were more frequently reconstructed by Billroth-I procedure than those following benign lesions (P < 0.001). Regarding reconstruction, RGC following Billroth-II reconstruction showed a longer interval between surgical procedures [P < 0.001; Billroth-II vs Billroth-I: 32 (5-51) vs 12 (2-36) years] and tumors were more frequently associated with benign disease (P < 0.001) than those following Billroth-I reconstruction. In tumor location of RGC, after Billroth-I reconstruction, RGC occurred more frequently near the suture line and remnant gastric wall. After Billroth-II reconstruction, RGC occurred more frequently at the anastomotic site. The duration of follow-up was significantly associated with the stage of RGC (P < 0.05). Patients diagnosed with early stage RGC such as stage I-II tended to have been followed up almost every second year., Conclusion: Meticulous follow-up examination and early detection of RGC might lead to a better prognosis. Based on the initial gastric disease and the procedure of reconstruction, an appropriate follow-up interval and programs might enable early detection of RGC.

Background/aims: The goal of our study was to determine the usefulness of the percutaneous placement of a drainage catheter using a one-step technique under guidance of computed tomography (CT) fluoroscopy., Methodology: Subjects were 11 patients (3 women, 8 men; mean age 65 years) who underwent percutaneous thoracic, abdominal, and pelvic drainage procedures for fluid collections between August 2010 and June 2011. The mean maximum diameter of the lesions was 53.8mm (range 30 to 82 mm) and the mean depth was 37.6mm (range 18 to 70mm). A drainage catheter that can be inserted by a one- step technique without a guide wire was used. The procedures were guided by use of a helical CT scanner that provided real-time fluoroscopic reconstruction., Results: Percutaneous drainage was successfully achieved in every procedure. Use of real-time CT-fluoroscopy and a drainage catheter that can be inserted with a one-step technique allowed rapid assessment of catheter placement. No patient had a serious complication related to the drainage procedure. The mean procedure time required to drain one lesion was 21.1 minutes (range 12 to 41 minutes)., Conclusions: Thoracic, abdominal, and pelvic drainage procedures using the one-step technique under CT-fluoroscopy guidance were accurate, safe and easy.

Tumor vascular invasion is one of the worst factors of metastasis and/or recurrence in hepatocellular carcinoma (HCC) patients after living donor liver transplantation (LDLT), leading to poor outcomes. We investigated the relevance between preoperative parameters and histological vascular invasion among HCC patients who underwent LDLT. We enrolled 27 HCC patients who underwent LDLT from September 2003 to February 2011 in our hospital. Their primary diseases were hepatitis C (n=16) hepatitis B (n=9), primary biliary cirrhosis (n=1), and cryptogenic liver cirrhosis (n=1). The 2 groups were positive (N=7) versus negative (N=20) histological vascular invasion. We compared the greatest size and numbers of tumors from preoperative enhanced computerized axial tomography (CAT) scans, preoperative serum levels of alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), as well as preoperative anticancer therapy. The preoperative greatest average diameter and numbers of tumor were 2.99 cm and 2.43, respectively, among positive patients, and 1.93 cm and 1.3, respectively, among patients with negative vascular invasion. The mean values of AFP and PIVKA-II were 3568.7 ng/mL and 2511.7 mAU/mL, respectively, among positive patients, and 812.8 ng/mL and 134.8 mAU/mL, respectively, among patients with negative vascular invasion. Five positive and 11 negative patients received preoperative anticancer therapy. Even if the tumor was within Milan criteria, namely, maximum size 3 cm and number of tumors 3, preoperative treatment may be a preoperative predictive factor for positive histological vascular invasion., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A boron-doped diamond (BDD) electrode was constructed as a water disinfector for the inactivation of water borne pathogens. The bactericidal effect of the disinfector was evaluated on artificially contaminated waters containing, respectively, Escherichia coli, Pseudomonas aeruginosa and Legionella pneumophila at high density. By treating the bacterial suspensions with 4 V of constant voltage between the BDD and the counter-electrode for 50 min, the population of E. coli and P. aeruginosa decreased from (10E + 7-8 colony-forming unit mL(-1)) to below the detection limits of the colony-formation method. Meanwhile, L. pneumophila were reduced to virtually zero when analyzed by fluorescence-based staining. The influences of production parameters (voltage, NaCl concentration and flow rate) on the disinfection kinetics of the BDD disinfector were examined with respect to operational conditions. Voltage was the most significant factor for adjusting the extent of electrolysis, followed by NaCl concentration and flow rate, to influence the disinfection efficiency. The disinfection of natural river water samples containing numerous microbes was performed for a practicability investigation of the BDD electrode. Approximately 99.99% bactericidal efficiency was confirmed by viability detection for E. coli and common germs in treated water. The results showed that the BDD electrode is a promising tool for various wastewater disinfections to combat waterborne diseases.

We investigated the prevalence of Salmonella in chicken meat from northern, central, and southern Japan. Between 2006 and 2008, 821 samples from these three regions were collected and examined. Salmonella isolates were detected in 164 (20.0%) of these samples, with 15 (10.0%) of 150, 113 (27.5%) of 411, and 36 (13.8%) of 260 recovered from the northern, central, and southern regions, respectively. We recovered 452 Salmonella isolates. From the isolates, 27 serovars were identified; the predominant serovars isolated were Salmonella Infantis (n=81), Salmonella Kalamu (n=56), and Salmonella Schwarzengrund (n=43). Of the 452 isolates, 443 (98.0%) were resistant to one or more antibiotics, and 221 (48.9%) showed multiple-antibiotic resistance, thereby implying that multiple-antibiotic resistant Salmonella organisms are widespread in chicken meat in Japan. Resistance to oxytetracycline was most common (72.6%), followed by dihydrostreptomycin (69.2%) and bicozamycin (49.1%). This study, the first to report Salmonella prevalence in chicken meat throughout Japan, could provide valuable data for monitoring and controlling Salmonella infection in the future., (Copyright ©, International Association for Food Protection)

We report a rare autopsy case of disseminated strongyloidiasis combined with cytomegalovirus co-infection involving a 68-year-old man, who was originally from Okinawa Prefecture in southern Japan, where strongyloidiasis occurs sporadically among the elderly. This patient was admitted with a diagnosis of drug eruption and hypereosinophilic syndrome. He was administered steroid therapy, but suffered complications of fever, respiratory distress, and pulmonary hemorrhaging. The autopsy findings showed disseminated strongyloidiasis in the alveolar spaces and the intestine and cytomegalovirus inclusion body foci in the lungs.

A nationwide survey was conducted to determine Salmonella prevalence in airborne dust from layer farms. Of the 4,090 layer farms in Japan, 203 were surveyed and 48 (23.6%) of these were positive for Salmonella. Salmonella isolation rates were higher in the eastern (24.3%), central (25.6%), western (23.9%), and southern (27.5%) prefectures than they were in the northern (13.3%) prefecture. We recovered 380 Salmonella isolates and identified 34 different Salmonella serovars. Salmonella Infantis was the most prevalent serovar (42 [11.1%] of 380), followed by Salmonella Agona (39 [10.3%] of 380), Salmonella Mbandaka (37 [9.7%] of 380), Salmonella Cerro (32 [8.4%] of 380), Salmonella Thompson (29 [7.6%] of 380), and Salmonella Braenderup (27 [7.1%] of 380). Of the 380 isolates, 273 (71.8%) were resistant to more than one antibiotic. Salmonella Infantis (41 [97.6%] of 42), Salmonella Agona (38 [97.4%] of 39), and Salmonella Mbandaka (34 [91.9%] of 37) showed the highest resistance rates. We found 18 different resistance patterns and the most common (179 [47.1%] of 273) was resistant to dihydrostreptomycin. One of the 13 Salmonella Hadar isolates was resistant to eight antibiotics. To investigate characteristics of Salmonella Agona, Salmonella Infantis, and Salmonella Mbandaka isolates across different prefectures, we performed pulsed-field gel electrophoresis by using XbaI and BlnI. The Salmonella Agona and Salmonella Mbandaka dendrograms were grouped into seven clusters, with 80 and 70% similarity, respectively. Because the Salmonella Infantis dendrogram showed low similarity, there is a possibility of genetic diffusion of this serovar across Japan. This report is the first to describe Salmonella contamination in airborne dust from layer farms in Japan. Our findings should be useful for future Salmonella infection monitoring and control.

A high-performance, environmentally friendly water treatment system was developed. The system consists mainly of an electrochemical and a photocatalytic oxidation unit, with a boron-doped diamond (BDD) electrode and TiO(2) photocatalyst, respectively. All electric power for the mechanical systems and the electrolysis was able to be provided by photovoltaic cells. Thus, this system is totally driven by solar energy. The treatment ability of the electrolysis and photocatalysis units was investigated by phenol degradation kinetics. An observed rate constant of 5.1 x 10(-3)dm(3)cm(-2)h(-1) was calculated by pseudo-first-order kinetic analysis for the electrolysis, and a Langmuir-Hinshelwood rate constant of 5.6 microM(-1)min(-1) was calculated by kinetic analysis of the photocatalysis. According to previous reports, these values are sufficient for the mineralization of phenol. In a treatment test of river water samples, large amounts of chemical and biological contaminants were totally wet-incinerated by the system. This system could provide 12L/day of drinking water from the Tama River using only solar energy. Therefore, this system may be useful for supplying drinking water during a disaster., ((c) 2009 Elsevier Ltd. All rights reserved.)

We tested whether the cultural background of raters influenced ratings of chimpanzee personality. Our study involved comparing personality and subjective well-being ratings of 146 chimpanzees in Japan that were housed in zoos, research institutes, and a retirement sanctuary to ratings of chimpanzees in US and Australian zoos. Personality ratings were made on a translated and expanded version of a questionnaire used to rate chimpanzees in the US and Australia. Subjective well-being ratings were made on a translated version of a questionnaire used to rate chimpanzees in the US and Australia. The mean interrater reliabilities of the 43 original adjectives did not markedly differ between the present sample and the original sample of 100 zoo chimpanzees in the US. Interrater reliabilities of these samples were highly correlated, suggesting that their rank order was preserved. Comparison of the factor structures for the Japanese sample and for the original sample of chimpanzees in US zoos indicated that the overall structure was replicated and that the Dominance, Extraversion, Conscientiousness, and Agreeableness domains clearly generalized. Consistent with earlier studies, older chimpanzees had higher Dominance and lower Extraversion and Openness scores. Correlations between the six domain scores and subjective well-being were comparable to those for chimpanzees housed in the US and Australia. These findings suggest that chimpanzee personality ratings are not affected by the culture of the raters.

Background: Because invasion to an adjacent organ (T4) indicates highly advanced disease, and most surgeons avoid esophagectomy, the prognostic impact of clinicopathologic factors for survival of these patients after esophagectomy has rarely been analyzed., Study Design: From 1960 to 2005, a total of 268 patients with esophageal squamous cell carcinoma underwent esophagectomy for pathologic T4 disease (pT4). The impact of clinicopathologic factors on survival was evaluated by univariate and multivariate analysis. Changes in surgical outcomes and longterm survival between the earlier period (1960 to 1989) and the later period (1990 to 2005) were analyzed., Results: Overall survival rates of all patients were 25% at 1 year, 10% at 3 years, and 5% at 5 years. The survival curve of the later group was significantly better than that of the earlier group (p < 0.01). Multivariate analysis indicated that venous invasion (hazards ratio, 1.76; 95% CI, 1.33 to 2.33, p < 0.01) and presence of a postoperative complication (hazards ratio, 2.62; 95% CI, 1.96 to 3.51, p < 0.01) were independent risk factors for poor overall survival. Presence of residual cancer was also an independent risk factor for poor cause-specific survival (hazards ratio, 2.40; 95% CI, 1.23 to 4.69, p=0.01). Venous invasion and intramural metastasis were risk factors for residual cancer. A total of 38 (14%) patients, 15 in the early period and 23 in the later period, underwent complete resection (R0). Although overall survival after R0 resection in the later period improved slightly, cancer-related survival rates were similar in both periods., Conclusions: Although overall survival of patients with pT4 improved after 1990, this improvement might be mainly dependent on curability of the resection.

Background: Recent reports have shown a correlation between extensive Mongolian spots and mucopolysaccharidosis type II (Hunter syndrome). However, a statistical survey of the incidence and natural history of extensive Mongolian spots among the patients with Hunter syndrome is lacking., Objectives: To determine the prevalence of extensive Mongolian spots, to determine the natural course of the spots according to age in Japanese patients with Hunter syndrome, and to compare them with the results obtained from the patients' brothers who did not have Hunter syndrome., Patients/methods: Fifty-two males with Hunter syndrome aged 3 to 40 years were studied. Twenty-five patients were examined in two clinics to determine the existence and characteristics of the spots. We interviewed their families about the spots in their neonates and the natural course of the spots according to their ages. The same survey was done among another 27 patients using a mailed questionnaire to their families. As control, we investigated 21 brothers of the patients by a mailed questionnaire to their families., Results: The extensive Mongolian spots are identified in almost all the infants with Hunter syndrome and disappear extremely later in their life. The lesions had a high incidence of deep-blue hyperpigmentation. Regardless of age, the overall incidence was 78%. All of the brothers who did not have Hunter syndrome had common-type Mongolian spots in neonates, which regressed during their childhood., Conclusion: Our results confirm a strong correlation between extensive Mongolian spots and Hunter syndrome for the Japanese population. The presence of extensive Mongolian blue spots should alert the physician to the possibility of Hunter syndrome.

Intrathecal baclofen administration is a fully established treatment for severe spasticity. However, it is scarcely known that Baclofen, an agonist of GABA-B receptor, has other potential effects on pain, restoration coma, dystonia, tetanus, and hypothalamic storm. Sporadic episodes of dramatic recovery from persistent vegetative state are reported after intrathecal administration of baclofen. There are also reports on the use of baclofen for neuropathic pain including poststroke central pain syndrome. Baclofen is also used for control of dystonia due to cerebral palsy or reflex sympathetic dystrophy. On the other hand, epidural spinal cord stimulation has been used for pain, spasticity, dystonia, or attempt to improve deteriorated consciousness, though the effects seem variable and modest. Similarity between baclofen and spinal cord stimulation is interesting in that both involve the spinal GABAergic system. Based on the 15-year personal experience of intrathecal baclofen, I would stress importance of this treatment not only for spasticity but also for other difficult neurological disorders.

Japan Aerospace Exploration Agency (JAXA) has developed a cell biology experiment facility (CBEF) and a clean bench (CB) as a common hardware in which life science experiments in the Japanese Experiment Module (JEM known as "Kibo") of the International Space Station (ISS) can be performed. The CBEF, a CO2 incubator with a turntable that provides variable gravity levels, is the basic hardware required to carry out the biological experiments using microorganisms, cells, tissues, small animals, plants, etc. The CB provides a closed aseptic operation area for life science and biotechnology experiments in Kibo. A phase contrast and fluorescence microscope is installed inside CB. The biological experiment units (BEU) are designed to run individual experiments using the CBEF and the CB. A plant experiment unit (PEU) and two cell experiment units (CEU type1 and type2) for the BEU have been developed.

The National Space Development Agency of Japan (NASDA) has more than 20 years of experience developing aquatic animal experiment facilities. We are now studying the next-generation aquatic animal experiment facility or the Aquatic Habitat (AQH) for both Space Shuttle and International Space Station use. A prototype breeding system was designed and tested. Medaka adult fish were able to mate and spawn in this closed circulatory breeding system, and the larvae grew to adult fish and spawned on the 45th day after hatching. The water quality-control system using nitrifying bacteria worked well throughout the medaka breeding test. For amphibians, we also conducted the African clawed toad (Xenopus laevis) breeding test with the same specimen chambers, although a part of circulation loop was opened to air. Xenopus larvae grew and completed metamorphosis successfully in the small specimen chamber. The first metamorphic climax started on the 30th day and was completed on the 38th day., (c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.)

Background: The definition of the degree of lymph node metastasis (n-classification) for gastric cancer differs greatly in the new Union Internationale Contre le Cancer--TNM classification (5th edition) and the Japanese gastric cancer classification (JGC). The feasibility of the new TNM classification is evaluated in comparison with the JGC., Methods: At Chiba University, 940 patients who underwent a gastrectomy were retrospectively classified into appropriate stages with both the TNM and JGC systems, and the survival curves of the respective stages were also compared., Results: Patients with 1 to 6 metastatic nodes (TNM-pN1) showed similar survival rates whether the metastases were limited to the perigastric area (JGC-n1) or reached distant areas (JGC-n2). The patients with node metastasis that was limited to the perigastric area (JGC-n1) had significantly different survival rates, depending on the number of metastatic nodes (TNM-pN1 or pN2, P = .022). A similar phenomenon was also observed in patients with TNM-N2 and JGC-n2. A multivariate analysis indicated the TNM N-classification, rather than the JGC n-classification, as an independent prognostic factor., Conclusions: The new TNM classification appears to be a better prognostic indicator than the JGC system for patients with gastric carcinoma.

The feasibility of the new classification of stage grouping by the Japanese Research Society for Gastric Cancer was evaluated. During the 22-year period between January 1975 and December 1996, a total of 1294 patients with primary gastric cancer underwent laparotomy at the Department of Surgery, Chiba University; 1222 had their lesions removed during the gastrectomy and 72 remained nonresected. Cases of direct operative death totaled 17 (1.3%). Five hundred patients (38.6%) died of a relapse of the original cancer and 42 (3.2%) died of other diseases within the followup period. Six patients (0.5%) were lost during the followup. The 5-year cumulative patient survival rates of the seven stages of the new stage grouping were distinctly proportional, and the differences were also statistically significant except between stages IIIb and IVa. The two major revised points in the new stage grouping, new classification of the depth of cancer invasion, and new stage grouping by a mosaic combination of the degree of invasion and lymph node metastasis were thus found to be reasonable based on the actuarial 5-year survival rates of the subgroups in the same stage. The present study also showed that the classification of stage IV still requires further discussion.