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Here we report the case of a 43-year-old Japanese woman with acute myelogenous leukemia who underwent 2 unrelated cord blood transplantations (UCBT), terminating in fatal disseminated tuberculosis (TB). The patient did not achieve remission despite intensive chemotherapy, and subsequently underwent UCBT with a standard conditioning regimen. However, engraftment was not achieved. Fifty days after the first UCBT, the patient underwent a second UCBT with a reduced-intensity conditioning regimen. She developed a pre-engraftment immune reaction, which responded well to prednisolone, and engraftment was documented. However, 50 days after the second UCBT, the patient presented with high fever and developed pneumonia despite antibiotic and antifungal treatments. Thereafter, Mycobacterium tuberculosis was detected in blood cultures and specimens of bronchoalveolar lavage, thus indicating disseminated TB. Despite anti-tuberculous treatment, she died on day 85. TB should always be considered as a possible diagnosis when treating febrile immunocompromised patients. [ABSTRACT FROM AUTHOR]

Abstract: We report a successful demonstration of a high S/N ratio spin flip chopper (SFC) system for pulsed neutron sources. The system consists of two SFCs and each SFC consists of a radio frequency (RF) flipper and Soller magnetic supermirrors. The aperture of the Soller mirror was 18mm in width and 20mm in height. The S/N ratio of the system was 306:1. This system is going to be installed to measure neutron lifetime precisely using the cold-neutron beam line, BL05 polarized-beam branch, at the Materials and Life Science Experimental Facility (MLF) in Japan Proton Accelerator Research Complex (J-PARC). [Copyright &y& Elsevier]

Background: The commercial availability of anamorelin, Japan's first therapeutic agent for cancer cachexia in 2021, led to an investigation into its prescription patterns at Toyama University Hospital. Objective: We aimed to analyze anamorelin prescription trends and outcomes among cancer cachexia patients. Methods: A retrospective study from July 2021 to December 2022 examined 88 cases, assessing demographics, cancer types, prescription locations, and meal intake changes. Results: Anamorelin usage was predominant during chemotherapy, especially for pancreatic cancer in outpatient settings. Approximately 30% experienced increased meal intake. Chemotherapy-initiated cases had a longer median duration (55 days) compared with best supportive care only cases (12 days). Conclusion: Anamorelin demonstrated significant prescription patterns, particularly during chemotherapy for pancreatic cancer in outpatient settings, suggesting potential efficacy enhancements when administered with chemotherapy in cancer cachexia management. The study underscores the importance of tailored approaches to optimize anamorelin's therapeutic benefits.

Background & Aims: PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 have been associated with an increased risk of liver-related events (LREs) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, we investigated the combined effects of these variants on LREs., Methods: The longitudinal multicenter cohort study enrolled 1178 patients with biopsy-proven MASLD. We calculated the genetic risk of hepatic fibrosis and LRE according to the impact of these variants., Results: Patients with genetic fibrosis scores of 2, 3, and 4 or 5 were at greater risk than patients with scores of 0 or 1, with odds ratios of 2.45 (95% CI, 1.27-4.74), 2.14 (95% CI, 1.17-3.94), and 2.54 (95% CI, 1.35-4.77), respectively. Multivariate analysis revealed that PNPLA3 and TM6SF2, but not HSD17B13, were associated significantly with LRE development. The hazard ratio of the genetic high-risk group for LRE was 1.91 (95% CI, 1.20-3.04). The higher risk of LRE development in the genetic high-risk group also was seen in patients with F ≥ 3 or Fibrosis-4 index > 2.67. The hazard ratios of the genetic high-risk group for LRE were greater in patients without obesity, without diabetes, and of younger age compared with patients with obesity, with diabetes, or of older age, respectively., Conclusions: This combination of MASLD-related genetic variants is useful for predicting LREs in Japanese patients with MASLD. The genetic risk according to these variants is useful for LRE risk assessment, especially in patients without metabolic risk factors or in younger patients in Japan., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Adenovirus is a major pathogen causing febrile illness among children. It may also cause acute encephalitis/encephalopathy. This study aimed to elucidate the clinical features of adenovirus-associated encephalitis/encephalopathy (AdVE) among children in Japan., Methods: A nationwide survey of children with AdVE was conducted. An initial survey was distributed among pediatricians to obtain information about children with AdVE treated between January 2014 and March 2019. A second survey was used to obtain the clinical information of children with AdVE from hospitals that responded to the initial survey and those identified from a literature search of the reported cases. We collected demographic data and information about symptoms of infection, neurological symptoms, laboratory parameters, treatment, and outcomes. Outcomes were determined using the Pediatric Cerebral Performance Category Score., Results: Clinical information was available for 23 children with a median age of 39 months. Two had preexisting neurological disorders and six had a history of febrile seizures. The outcome was good in 15 patients and poor in eight patients. Serum lactate dehydrogenase, glucose, and ammonia levels were higher among children with a poor outcome compared to those with a good outcome. Clinically mild encephalitis/encephalopathy with a reversible splenial lesion was the most common type (n = 8), followed by acute encephalopathy with biphasic seizures and late reduced diffusion (n = 7)., Conclusion: A prior history of febrile seizures was frequent in children with AdVE. Several different subtypes of acute encephalopathy were seen in children with AdVE, and the outcome was poor in those with acute encephalopathy with biphasic seizures and late reduced diffusion and hemorrhagic shock and encephalopathy syndrome. Elevated lactate dehydrogenase, glucose, and ammonia levels on admission were found to correlate with a poor outcome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background & Aims: PNPLA3 rs738409 has been associated with an increased risk of liver-related events in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the epidemiology of NAFLD and the impact of PNPLA3 on prognosis in Japan., Methods: A longitudinal multicentre cohort study, the JAGUAR study, includes 1550 patients with biopsy-proven NAFLD in Japan. We performed genetic testing and evaluated outcomes from this cohort. Liver-related events were defined as hepatocellular carcinoma (HCC) and decompensated liver cirrhosis events., Results: During follow-up (median [range], 7.1 [1.0-24.0] years), 80 patients developed HCC, 104 developed liver-related events, and 59 died of any cause. The 5-year rate of liver-related events for each single-nucleotide polymorphism was 0.5% for CC, 3.8% for CG, and 5.8% for GG. Liver-related deaths were the most common (n = 28); only three deaths were due to cardiovascular disease. Multivariate analysis identified carriage of PNPLA3 CG/GG (hazard ratio [HR] 16.04, p = .006) and FIB-4 index >2.67 (HR 10.70, p < .01) as predictors of liver-related event development. No HCC or liver-related death was found among patients with PNPLA3 CC. There was a significantly increased risk of HCC, liver-related events, and mortality for CG/GG versus CC, but no difference between the CG and GG genotypes., Conclusions: In Japanese individuals, the main cause of death from NAFLD is liver-related death. The greater risk of liver-related events incurred by PNPLA3 G allele was shown in Japan. Risk stratification for NAFLD in Japan is best accomplished by integrating PNPLA3 with the FIB-4 index., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A COVID-19 patient surge in Japan from July to September 2021 caused a mismatch between patient severity and bed types because hospital beds were fully occupied and patient referrals between hospitals stagnated. Japan's predominantly private healthcare system lacks effective mechanisms to coordinate healthcare providers to address the mismatch. To address the surge, in August 2021, Tokyo Saiseikai Central Hospital started a scheme to exchange patients with other hospitals to mitigate the mismatch. In this article, we outline a retrospective observational study using medical records from a tertiary care medical center that treated severe COVID-19 cases. We describe daily patient admissions to our hospital's COVID-19 beds from July to September 2021, and compared the moving average of daily admissions before and after the exchange scheme was introduced. Bed occupancy reached nearly 100% in late July when the patient surge began and continued to exceed 100% in August when the surge peaked. However, the average daily admission did not decrease in August compared with July: the median daily admission (25th to 75th percentile) during each period was 2 (1 to 2.5) in late July and 3 (2 to 4) in August. The number of patients referred in from secondary care hospitals and the number of patients referred out was balanced in August. During the patient surge, the exchange scheme enabled the hospital to maintain and even increase the number of new admissions despite the bed shortage. Coordinating patient referrals in both directions simultaneously, rather than the usual 1-way transfer, can mitigate such mismatches.

Background: Empathy, consisting of cognitive empathy and affective empathy, is essential for creating relationships with others. Since the genetic polymorphism of oxytocin receptor (OXTR) and arginine-vasopressin V1B receptor (AVPR1B) relate to prosocial behavior and empathy, it would need to innovate strategies for treating human empathy by considering individual genetic variations. Physical activity is expected as a possible strategy; here, we investigated the influences of genetic polymorphisms in OXTR SNP rs53576 and AVPR1B SNP rs28373064, on the relationships of self-reported empathy with physical activity., Methods: The saliva is collected from a hundred Japanese college students for determining the individual polymorphism of OXTR SNP rs53576 (AA, AG, or GG genotype) and AVPR1B SNP rs28373064 (TT, TC, or CC genotype). In addition, the participants' self-reported cognitive and affective empathy, amounts of physical activity, and sitting time were evaluated with questionaries., Results: The participants with OXTR SNP rs53576 GG genotype showed a significant negative correlation between sitting time and cognitive empathy adjusted by age, gender, and sports experience. Further, there was a trend to correlate between physical activity amounts and cognitive empathy in the participants carrying the G variant in OXTR SNP rs53576 (AG or GG). As for AVPR1B SNP rs28373064, the persons with TT genotype exhibited a negative correlation trend between sitting time and cognitive empathy., Conclusions: There are possible correlations between the self-reported cognitive empathy and physical activity amounts in the persons carrying the G variant of OXTR rs53576 or with the TT genotype for AVPR1B SNP rs28373064., (Copyright © 2022. Published by Elsevier Inc.)

To estimate the health-promoting effects of Lacticaseibacillus paracasei (previously Lactobacillus casei ) strain Shirota (LcS) that reached the lower gastrointestinal tract alive, we investigated the characteristics of gut microbiome, organic acid profiles, defecatory symptoms and serum viral antibody indexes of healthy Japanese adults between the group in whom live LcS was detected or not from stool. The β-diversity index of the gut microbiome constituted a significant difference between the live-LcS-detected-group (LLD) and the live-LcS-not-detected-group (LLnD). In the LLD, the Bifidobacteriaceae, Lactobacillaceae , and Coriobacteriaceae counts were significantly higher, and the succinate concentration was significantly lower than that in the LLnD. The serum herpes simplex virus (HSV) immunoglobulin (Ig)M antibody index in the LLD tended to be lower than that of the LLnD in HSV IgG-positive subjects. Of the LLD, those in the fermented milk products containing LcS (FML)-high-frequency-group (FML-HF) and those in the FML-low-frequency-group (FML-LF) had different gut microbiome and organic acid profiles. However, the pattern of differences between FML-HF and FML-LF was dissimilar those between LLD and LLnD. In contrast, among subjects with FML-LF, those in the group with LLD in stool (LF-LLD) and those in the LLnD in stool (LF-LLnD) showed a similar pattern of differences in their gut microbiome and organic acid profiles as those in the LLnD and LLD. The LLD and LF-LLD commonly had lower caloric and carbohydrate intakes from the diet than their respective control groups. In this study, we found that the presence of live LcS in stool is associated with a healthy gut environment and inhibition of the reactivation of latently infected viruses in the host. However, these health-promoting effects on the host were not related to the frequency of FML intake. Furthermore, dysbiosis of the gut microbiome and diet including caloric intake was related to the viability of ingested LcS in the gut.

Objective: To determine the efficacy and safety of fremanezumab administration in Japanese and Korean patients with chronic migraine (CM)., Background: Available preventive treatments for CM are limited by various efficacy and safety issues. Fremanezumab, a monoclonal antibody that targets the calcitonin gene-related peptide pathway involved in migraine pathogenesis, has been shown to be effective and well tolerated in large-scale, international Phase 3 trials., Methods: Randomized, placebo-controlled trial of patients with CM who received subcutaneous fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), or matching placebo. Primary endpoint was the mean change from baseline in the monthly (28-day) average number of headache days of at least moderate severity during the 12 weeks after the first dose., Results: Among 571 patients randomized (safety set, n = 569; full analysis set, n = 566), the least-squares mean (±standard error [SE]) reduction in the average number of headache days of at least moderate severity per month during 12 weeks was significantly greater with fremanezumab monthly (-4.1 ± 0.4) and fremanezumab quarterly (-4.1 ± 0.4) than with placebo (-2.4 ± 0.4). The difference from the placebo group in the mean change (95% confidence interval [CI]) was -1.7 days (-2.54, -0.80) for the fremanezumab monthly group and -1.7 days (-2.55, -0.82) for the fremanezumab quarterly group (p < 0.001 vs. placebo for both fremanezumab groups). The percentage of patients with a ≥50% reduction in the average number of headache days of at least moderate severity per month (response rate) was higher with fremanezumab monthly (29.0%) and fremanezumab quarterly (29.1%) than with placebo (13.2%) in addition to other improvements in secondary endpoints, including reduction of acute medication use (mean change from baseline during 12-week period ± SE: fremanezumab monthly, -3.7 ± 0.4; fremanezumab quarterly, -3.9 ± 0.4; placebo, -2.4 ± 0.4) and improvements in disability scores (mean change from baseline in six-item Headache Impact Test score at 4 weeks after third injection ± SE: fremanezumab monthly, -8.1 ± 0.7; fremanezumab quarterly, -8.0 ± 0.7; placebo, -6.5 ± 0.7). Fremanezumab was well tolerated with a similar incidence of adverse events including injection-site reactions as placebo (patients with at least one treatment-emergent adverse event: fremanezumab total, n = 232 [61.4%]; placebo, n = 118 [61.8%])., Conclusion: Fremanezumab effectively prevents CM in Japanese and Korean patients and was well tolerated. No safety signal was detected., (© 2021 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Background: Although type 2 diabetes mellitus (T2DM) is a known risk factor for hepatocellular carcinoma (HCC) development, the annual incidence in diabetes patients is far below the threshold of efficient surveillance. This study aimed to elucidate the risk factors for HCC in diabetic patients and to determine the best criteria to identify surveillance candidates., Methods: The study included 239 patients with T2DM who were diagnosed with non-viral HCC between 2010 and 2015, with ≥ 5 years of follow-up at diabetes clinics of 81 teaching hospitals in Japan before HCC diagnosis, and 3277 non-HCC T2DM patients from a prospective cohort study, as controls. Clinical data at the time of and 5 years before HCC diagnosis were collected., Results: The mean patient age at HCC diagnosis was approximately 73 years, and 80% of the patients were male. The proportion of patients with insulin use increased, whereas the body mass index (BMI), proportion of patients with fatty liver, fasting glucose levels, and hemoglobin A1c (HbA1c) levels decreased significantly in 5 years. In the cohort study, 18 patients developed HCC during the mean follow-up period of 4.7 years with an annual incidence of 0.11%. Multivariate logistic regression analyses showed that the FIB-4 index was an outstanding predictor of HCC development along with male sex, presence of hypertension, lower HbA1c and albumin levels, and higher BMI and gamma-glutamyl transpeptidase levels. Receiver-operating characteristic analyses showed that a FIB-4 cut-off value of 3.61 could help identify high-risk patients, with a corresponding annual HCC incidence rate of 1.1%., Conclusion: A simple calculation of the FIB-4 index in diabetes clinics can be the first step toward surveillance of HCC with a non-viral etiology.

Although diet is an important factor influencing gut microbiota, there are very few studies regarding that relationship in Japanese people. Here, we analyzed the relationship between habitual dietary intake surveyed by food frequency questionnaire and the quantitative features of gut bacteria by quantitative PCR and next generation sequencer in 354 healthy Japanese adults. The α-diversity of gut microbiota was positively correlated with the intake of mushrooms and beans and negatively correlated with the intake of grains. The β-diversity was significantly associated with the intake of fruits, mushrooms, seaweeds, seafoods, and alcoholic beverages. Multiple linear regression analysis of the relationship between food groups associated with the diversity of gut microbiota and the number of gut bacteria at the genus level found 24 significant associations, including a positive association between alcoholic beverages and the number of Fusobacterium . These results support that habitual dietary intake influenced the diversity of gut microbiota and was strongly associated with the number of specific gut bacteria. These results will help us to understand the complex relationship between habitual diet and gut microbiota of the Japanese.

Background and Aim: The presence of cirrhosis is an important factor for the management of patients with hepatitis C virus (HCV) infection and it determines the duration of treatment for HCV with the direct-acting antiviral (DAA) regimen of glecaprevir (GLE) and pibrentasvir (PIB), that is, 8 or 12 weeks, if patients do not have a history of DAA failure. However, in real-world settings, determination of cirrhosis depends on the discretion of the attending hepatologists, and it is unclear whether compensated cirrhosis was homogenously diagnosed or not. In this study, we investigated the real-world diagnosis of cirrhosis by characterizing DAA-naïve patients who underwent a 12-week GLE/PIB regimen in whom cirrhosis was diagnosed, comparing their characteristics with those of patients who underwent an 8-week regimen in whom cirrhosis was absent., Methods: In a large, multicenter cohort study, we compared background characteristics and treatment outcomes among DAA-naïve patients who underwent an 8-week versus a 12-week GLE/PIB regimen., Results: Among 977 patients enrolled, 296 (30.3%) were determined to have cirrhosis and underwent a 12-week regimen. Some patient characteristics largely overlapped between the two groups, including liver fibrosis indices. Sustained viral response rates were similar between groups after adjusting liver fibrosis index with propensity score matching., Conclusion: Although adequately diagnosed, the determination of cirrhosis varied widely among institutions or by hepatologists in real-world settings, and the severity of liver fibrosis overlapped significantly between patients in whom compensated cirrhosis was determined to be present and patients in whom cirrhosis was absent. Virologic efficacy was similar after adjusting for the degree of liver fibrosis., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Type 2 diabetes (T2D) is closely associated with nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to cirrhosis, hepatocellular carcinoma (HCC), and hepatic decompensation. Patients with T2D have twice the risk of HCC incidence compared with those without T2D. Because the hepatic fibrosis grade is the main determinant of mortality in patients with NAFLD, identifying patients with advanced fibrosis using non-invasive tests (NITs) or imaging modalities is crucial. Globally, the fibrosis-4 index (FIB-4 index), NAFLD fibrosis score, and enhanced liver fibrosis test have been established to evaluate hepatic fibrosis. Two-step algorithms using FIB-4 index as first triaging tool are globally accepted. It remains unknown which kinds of NITs or elastography are best as the second step tool. In Japan, type IV collagen 7s or the CA-fibrosis index (comprising type IV collagen 7s and aspartate aminotransferase (AST)) is believed to precisely predict advanced fibrosis in NAFLD. Patients with NAFLD who have high non-invasive test results should be screened for HCC or esophageal varices. Risk factors of rapid fibrosis progression in NAFLD includes age, severe obesity, presence of T2D, menopause in women, and a patatin-like phospholipase domain containing the 3 GG genotype. Patients with NAFLD who have these risk factors should be intensively treated with lifestyle modification or pharmacotherapies for preventing liver-related mortality.

Background: In clinical trials, a pangenotype direct-acting antiviral (DAA) regimen consisting of glecaprevir (GLE) and pibrentasvir (PIB) exhibited high virologic efficacy and tolerability in patients with hepatitis C virus (HCV) infection. This study sought to confirm these findings in real-world settings, focusing on patients with cirrhosis, history of DAA failure, or HCV genotype 3 who were treated with a 12-week regimen in a large multicenter study from Japan., Methods: In a nationwide multicenter prospective cohort study, we analyzed background characteristics, tolerability, and treatment outcome of patients who underwent a 12-week GLE/PIB regimen., Results: Of 1190 patients, 509 (42.8%) underwent the 12-week regimen, and the remaining patients underwent an 8-week regimen. The rate of sustained virologic response (SVR) of patients treated with the 12-week regimen was 99.0%, comparable with that of patients treated with the 8-week regimen. The adverse events were observed in 29.1% of patients. The main adverse event was pruritus, which was observed in 14.7%. Ten patients (2.0%) discontinued therapy during treatment period., Conclusion: The 12-week GLE/PIB regimen was well-tolerated with high virologic efficacy in patients with cirrhosis, experience of DAA, or HCV genotype 3; tolerability and SVR rate were comparable with those of DAA-naïve, non-cirrhotic, non-genotype 3 patients who underwent 8-week regimen., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Direct-acting anti-virals (DAAs) have markedly improved the effectiveness of anti-viral therapy for chronic hepatitis C (CHC) patients. In a phase III trial in Japan, treatment with the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir (G/P) resulted in a small number of patients with refractory factors. We aimed to evaluate the effectiveness and safety of G/P, especially among patients with these refractory factors, and the influence of these factors on treatment., Methods: In a prospective, multicenter study involving 33 medical institutions, 1439 patients were treated with G/P, and their efficacy, safety, and most frequent adverse effects (AEs) were analyzed., Results: Overall SVR12 rates were 99.1% (1397/1410) in the per-protocol-analysis, and genotype sustained virologic response SVR12 rates were: genotype 1, 99.4% (707/711); genotype 2, 99.4% (670/674); genotype 3, 80.0% (16/20). DAA-naïve patients (p = 0.008) with HCV genotype except 3 (genotype 1 vs. 3, p = 2.68 × 10 -5 ; genotype 2 vs. 3, p = 3.28 × 10 -5 ) had significantly higher SVR12 rates. No significant difference was observed between CKD stage 1-3 (99.1% [1209/1220]) and chronic kidney disease (CKD) stage 4-5 (98.9% [188/190]) patients, or between cirrhotic (99.0% [398/402]) and non-cirrhotic (99.1% [999/1008]) patients. Multiple logistic regression analysis revealed that genotype 3 [OR 33.404, 95% CI (7.512-148.550), p value (p = 4.06 × 10 -5 )] and past experience of IFN-free DAAs [OR 3.977, 95% CI (1.153-13.725), p value (p = 0.029)] were both significantly independent predictors of non-SVR12. AEs were reported in 28.2% of patients, and 1.6% discontinued treatment owing to drug-related AEs. AEs were significantly higher in CKD stage 4-5 (41.6% [79/190]) than CKD stage 1-3 (26.1% [319/1220]) patients (p = 2.00 × 10 -5 ). AEs were also significantly higher in cirrhotic (38.6% [155/402]) than in non-cirrhotic (24.1% [243/1008]) (p = 2.91 × 10 -18 ) patients., Conclusions: G/P regimen is highly effective and safe to treat CHC patients even with refractory factors such as CKD and advanced liver fibrosis. However, patients with past experience of IFN-free DAA treatment and genotype 3, CKD stage 4 or 5, and advanced liver fibrosis should be more closely observed.

To assess compliance with the Japanese antiemetic guidelines for chemotherapy-induced nausea and vomiting (CINV), the frequencies of CINV occurrence and use of antiemetic rescue medications were examined in patients with hematological malignancy. A total of 40 patients with hematologic malignancy were eligible in this study. This study was performed in the Department of Hematology, Kyushu University Hospital, as a subgroup analysis from a nationwide, multicenter prospective cohort study conducted by the CINV Study Group of Japan. In the patients with hematological malignancy, the guideline compliance rate was 45 %. Five patients (22.7 %) experienced vomiting during the observation period after receiving non-guideline-consistent antiemetic prophylaxis, whereas no patient experienced vomiting after receiving guideline-consistent antiemetic prophylaxis. The study was not sufficiently powered to reach a statistical significance in its frequency of occurrence between the compliance and non-compliance groups. In the entire study period, 8 out of 40 patients required rescue medication, but there was no association between the status of compliance and the antiemetic guidelines. A total of 22 (55.0 %) patients achieved complete response, which was defined as no vomiting and no use of antiemetic rescue medication, during the study period. The rate of compliance with the prophylactic antiemetic treatment guidelines seemed to be low in patients with hematological malignancy, although the status of the guideline compliance did not always influence the antiemetic effects.

Background: Norovirus is a major pathogen of gastroenteritis and is known to cause encephalitis/encephalopathy. The aim of this national survey was to clarify the clinical features of norovirus-associated encephalitis/encephalopathy (NoVE) among children in Japan., Methods: A nationwide survey of children with NoVE was conducted using a structured research form. The initial survey asked pediatricians about children with NoVE treated between January 2011 and March 2016. The second survey obtained patient information from two sources: hospitals that responded to the initial survey and those identified as having treated cases from a literature search., Results: Clinical information was available for 29 children. Their median age was 2 y 8 m. The outcome was good in 13 patients and poor in 15. The interval between the onset of gastrointestinal symptoms and that of encephalitis/encephalopathy was significantly shorter in those with a poor outcome. At the onset of an elevated serum creatinine level and an abnormal blood glucose level were correlated with a poor outcome. Regarding the subtypes of encephalitis/encephalopathy, acute encephalopathy with biphasic seizures and late reduced diffusion and hemorrhagic shock and encephalopathy syndrome were frequent., Conclusion: The outcome of children with NoVE was poor. Early onset of neurological symptoms, an elevated serum creatinine level, and an abnormal blood glucose level were associated with a poor outcome. No effective treatment was identified and this should be the subject of future studies., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Secukinumab, a fully human monoclonal antibody neutralizing interleukin-17A, has been shown to have significant efficacy in the treatment of moderate to severe psoriasis. Long-term (3-year) efficacy and safety of secukinumab in Japanese patients with moderate to severe psoriasis were evaluated in an extension study of a large phase 3 global study (SCULPTURE). In the core study, 52 Japanese patients with 75% improvement of Psoriasis Area and Severity Index (PASI-75) response at week 12 were re-randomized to a fixed interval (FI; every 4 weeks) schedule and retreatment as needed (RAN), in which patients received placebo until start of relapse, at which time secukinumab was reinitiated. Fifty Japanese patients completed the 52-week core study, and 47 patients entered the extension study with the same double-blind regimens up to week 152. All patients in the secukinumab 300 mg FI and seven patients in 150 mg FI groups completed 3 years of treatment. PASI-90 and -100 at the end of year 3 were achieved in 69.2% and 53.8%, respectively, in 300 mg FI and 42.9% and 42.9%, respectively, in 150 mg FI, indicating high sustained response in 300 mg FI. Mean absolute PASI was continually low in 300 mg FI and numerically higher in 150 mg FI. Dermatology Life Quality Index of 0/1 was maintained by approximately two-thirds of 300 mg FI patients, and all EuroQoL 5-Dimension Health Questionnaire domain measures were also improved. FI dosing was consistently more efficacious than RAN. The safety profile of secukinumab remained favorable, with no new safety concerns identified., (© 2019 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Background: We reported a cross-sectional study on causes of liver injury in Japanese type 2 diabetes mellitus (T2D) patients (JG 2013). We assessed overall and cause-specific mortality risk during follow-up of patients enrolled in JG 2013., Methods: This was a longitudinal, multicenter cohort study. Of the 5642 Japanese T2D patients who visited T2D clinics of nine hospitals in the original study, 3,999 patients were followed up for an average of 4.5 years. Expected deaths in T2D patients were estimated using age-specific mortality rates in the general population (GP) of Japan. Standardized mortality ratios (SMRs) were calculated to compare mortality between T2D patients and GP., Results: All-cancer mortality was significantly higher in T2D patients than in the GP [SMR 1.58, 95% confidence interval (CI) 1.33-1.87]. Among malignancies, hepatocellular carcinoma (HCC) conferred the highest mortality risk in T2D patients (SMR 3.57, 95% CI 2.41-5.10). HCC-associated mortality risk in T2D patients remained significantly high (SMR 2.56, 95% CI 1.64-3.97) after adjusting for high positivity rates of hepatitis B surface antigen (1.7%) and anti-hepatitis C virus (5.3%). In T2D patients with platelet counts < 200 × 10 3 /μl, SMR of HCC increased from 3.57 to 6.58 (95% CI 4.34-9.58). T2D patients with platelet count > 200 × 10 3 /μl showed no increase in mortality risk (SMR 0.68) of HCC., Conclusions: HCC-associated mortality risk was the highest among all cancers in Japanese T2D patients. Regular follow-up may be important for T2D patients with platelet counts < 200 × 10 3 /μl for early detection of HCC.

Chemotherapy-induced nausea and vomiting (CINV) are generally evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE). The Multinational Association for Supportive Care in Cancer (MASCC) developed the MASCC Antiemesis Tool (MAT) to facilitate recognition for CINV between patients and oncology specialists. In the present study, MAT and CTCAE were comparatively assessed in Japanese patients with hematological malignancies. A total of 61 patients were eligible for this study. The CTCAE data were collected from an electronic medical record system. The patients were asked to complete the Japanese version of MAT in the hospital, on the first and fourth days after the start of chemotherapy. The percentages of patients in whom nausea was completely controlled, with severity scores of zero, ranged from 70.5 to 82.0% for CTCAE and from 59.0 to 75.4% for MAT, during the first five days after the chemotherapy. The percentages of patients who had no vomiting ranged from 93.4 to 96.7% for CTCAE and from 90.2 to 98.4% for MAT. During the observation periods, the day-to-day response profiles of patients who received antiemetic treatment were comparable between CTCAE and MAT cohorts, and these two assessment tools showed good, positive correlations for nausea severity scores. The present study shows that the MAT is a useful tool for assessing the severity of CINV in patients with hematological malignancy, is comparable to CTCAE, and facilitates the identification of poor cancer care conditions by medical staff.

Generalized pustular psoriasis (GPP) is a severe inflammatory skin disease characterized by the presence of sterile pustules covering almost the entire body and systemic symptoms such as fever. Secukinumab, a fully human-recombinant anti-interleukin-17A monoclonal antibody was indicated for psoriasis vulgaris and psoriatic arthritis in Japan but is not yet investigated for GPP. In this phase III, open-label multicenter single arm study, the efficacy and safety of secukinumab as monotherapy or with co-medication was evaluated in 12 Japanese patients with GPP. All the patients received secukinumab 150 mg s.c. at baseline, week 1, 2, 3 and 4, and then every 4 weeks. Two non-responders were up-titrated to 300 mg. Change in GPP severity from baseline was evaluated by clinical global impression (CGI) categorized as "worsened", "no change", "minimally improved", "much improved" or "very much improved". Treatment success was achieved by 83.3% (n = 10) of patients at week 16 (primary end-point) with CGI evaluated as "very much improved" (n = 9) and "much improved" (n = 1). Moreover, the area of erythema with pustules improved as early as week 1 and resolved by week 16 in most of the patients. The improvements were sustained throughout 52 weeks. Over the 52-week treatment period, secukinumab was well tolerated with no unexpected safety signals. Nasopharyngitis, urticaria, diabetes mellitus and arthralgia were the frequent adverse events reported. The data from this study shows that secukinumab can become one of the potent treatment options for GPP., (© 2016 Japanese Dermatological Association.)

Aripiprazole once-monthly (AOM) was previously approved for treatment of schizophrenia as monthly injections in the gluteal muscle. The deltoid muscle provides a more accessible injection site. The present study was conducted in Japanese schizophrenia patients as a 24-week, open-label trial that assessed the pharmacokinetics and safety of 5 sequential doses of AOM 400 mg (AOM 400) once every 4 weeks administered in the deltoid muscle. Patients treated with an oral atypical antipsychotic (other than aripiprazole) continued to receive their pre-study medication up to 14 days after the first AOM 400 injection. The completion rate was 76.5% (n = 13/17). Mean aripiprazole plasma C(min) almost reached steady-state by the fourth AOM 400 injection. After the fifth AOM 400 injection, mean aripiprazole AUC(28d), C(max) and C(min) were 165 μg x h/ml, 331 ng/ml and 201 ng/ml, respectively, which were similar to previously published pharmacokinetic parameters after the fifth gluteal injection of AOM 400. The most common treatment-emergent adverse event (TEAE) was injection site pain (35.3%). Most TEAEs were classified as mild in intensity. In conclusion, the deltoid injection of AOM can be considered an alternative route of administration, as deltoid and gluteal injections are interchangeable in terms of aripiprazole plasma concentrations, with no additional safety issues.

Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock, multi-organ failure, and high mortality. In Japan, appropriate notification measures based on the Infectious Disease Control law are mandatory for cases of STSS caused by β-haemolytic streptococcus. STSS is mainly caused by group A streptococcus (GAS). Although an average of 60-70 cases of GAS-induced STSS are reported annually, 143 cases were recorded in 2011. To determine the reason behind this marked increase, we characterized the emm genotype of 249 GAS isolates from STSS patients in Japan from 2010 to 2012 and performed antimicrobial susceptibility testing. The predominant genotype was found to be emm1, followed by emm89, emm12, emm28, emm3, and emm90. These six genotypes constituted more than 90% of the STSS isolates. The number of emm1, emm89, emm12, and emm28 isolates increased concomitantly with the increase in the total number of STSS cases. In particular, the number of mefA-positive emm1 isolates has escalated since 2011. Thus, the increase in the incidence of STSS can be attributed to an increase in the number of cases associated with specific genotypes.

Infection with Streptococcus agalactiae has long been recognized in infants. In recent years, S. agalactiae is an important cause of morbidity and mortality among adults and among those with underlying medical condition. Several cases of GBS infection and more fulminant disease similar to streptococcal toxic shock syndrome have recently been reported. We report here that 19 S. agalactiae strains were isolated from streptococcal toxic shock-like syndrome cases involving adult patients in Japan between 2009 and 2013. The average age of the patients was 66.3 years. At least one underlying disease was present in 47.4% (9/19) of the patients. The most prevalent serotype among these strains was Ib. All serotype Ib strains belonged to clonal complex 10 and were ciprofloxacin resistant. In contrast, all strains were susceptible to penicillin G, ampicillin, cefazolin, cefotaxime, imipenem, panipenem, and linezolid. The characteristic type distributions of streptococcal toxic shock-like syndrome isolates differed between isolates obtained from vaginal swabs of women and infants with invasive infections., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Data regarding clinical efficacy of thrombectomy in patients with acute myocardial infarction (AMI) have been still limited in Japan. Using the AMI-Kyoto Multi-Center Risk Study database, the clinical background characteristics, angiographic findings, primary percutaneous coronary intervention (PCI) results and in-hospital prognoses were retrospectively compared between AMI patients with totally occluded infarct-related artery (IRA) (TIMI flow grade 0) undergoing thrombus aspiration during primary PCI (with-aspiration patients, n = 568) and those without thrombus aspiration (without-aspiration patients, n = 266). The with-aspiration patients were more likely to have higher TIMI grade in the IRA immediately after primary PCI, and had a lower in-hospital mortality rate than the without-aspiration patients. According to a multivariate analysis, thrombectomy as well as stent usage was found to be independent predictor of final TIMI flow grade ≥2 in the IRA, and the final TIMI flow grade ≥2 in the IRA was found to be an independent factor for in-hospital survival. These results suggest that among real-world, unselected Japanese AMI patients with totally occluded IRA on initial coronary angiography, thrombus aspiration is an effective adjunctive therapy during primary PCI to improve final epicardial coronary flow in the IRA, which might lead to better in-hospital prognosis.

Consolidation therapy for patients with multiple myeloma (MM) has been widely adopted to improve treatment response following autologous stem cell transplantation. In this study, we retrospectively analyzed the safety and efficacy of combination regimen of bortezomib, thalidomide, and dexamethasone (VTD) as consolidation therapy in 24 Japanese patients with newly diagnosed MM. VTD consisted of bortezomib at a dose of 1.3 mg/m(2) and dexamethasone at a dose of 40 mg/day on days 1, 8, 15, and 22 of a 35-day cycle, with daily oral thalidomide at a dose of 100 mg/day. Grade 3-4 neutropenia and thrombocytopenia were documented in four and three patients (17 and 13 %), respectively, but drug dose reduction due to cytopenia was not required in any case. Peripheral neuropathy was common (63 %), but severe grade 3-4 peripheral neuropathy was not observed. Very good partial response or better response (≥VGPR) rates before and after consolidation therapy were 54 and 79 %, respectively. Patients had a significant probability of improving from

In April and May 2011, there was a serious food-poisoning outbreak in Japan caused by enterohemorrhagic Escherichia coli (EHEC) strains O111:H8 and O157:H7 from raw beef dishes at branches of a barbecue restaurant. This outbreak involved 181 infected patients, including 34 hemolytic-uremic syndrome (HUS) cases (19%). Among the 34 HUS patients, 21 developed acute encephalopathy (AE) and 5 died. Patient stool specimens yielded E. coli O111 and O157 strains. We also detected both EHEC O111 stx2 and stx-negative E. coli O111 strains in a stock of meat block from the restaurant. Pulsed-field gel electrophoresis (PFGE) and multilocus variable-number tandem-repeat analysis (MLVA) showed that the stx-negative E. coli O111 isolates were closely related to EHEC O111 stx2 isolates. Although the EHEC O157 strains had diverse stx gene profiles (stx1, stx2, and stx1 stx2), the PFGE and MLVA analyses indicated that these isolates originated from a single clone. Deletion of the Stx2-converting prophage from the EHEC O111 stx2 isolates was frequently observed during in vitro growth, suggesting that strain conversion from an EHEC O111 stx2 to an stx-negative strain may have occurred during infection., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

A microagglutination (MA) assay to identify antibodies to Escherichia coli O111 and O157 was conducted in sera collected from 60 patients during a food-poisoning outbreak affecting 181 patients in Japan which was caused by the consumption of contaminated raw beef. Enterohemorrhagic E. coli (EHEC) O111:H8 and/or O157:H7 was isolated from the stools of some of the patients, but the total rate of positivity for antibodies to O111 (45/60, 75.0%) was significantly higher than that for antibodies to O157 (10/60, 16.7%). The MA titers of antibodies to O111 measured in patients with hemolytic-uremic syndrome and bloody diarrhea were higher than those measured in patients with only diarrhea. In patients from whose stool no isolates of E. coli O111 and O157 were obtained, the positive antibody detection rates were 12/19 (63.2%) for O111 and 2/19 (10.5%) for O157, and the MA titers of antibodies to O111 measured were higher than those to O157. Similarly, the MA titers of antibodies to O111 were significantly higher than those to O157, regardless of the other groups, including groups O111, O111 and O157, and O157. These serodiagnosis results suggest that EHEC O111:H8 stx2 played a primary role in the pathogenesis of this outbreak. Furthermore, our findings suggest that the isolates from the patients' stool specimens were not always the major causative pathogen in patients with multiple EHEC infections, because the sera from patients from whose stools only O157 was isolated were positive for antibodies to O111. Measuring antibodies to E. coli O antigen is helpful especially in cases with multiple EHEC infections, even with a non-O157 serotype.

Cardiorenal anemia syndrome has recently been receiving greater attention; however, data regarding the relationship between chronic kidney disease (CKD)/anemia on presentation and in-hospital outcome in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are still limited in Japan.A total of 1,447 primary PCI-treated AMI patients were classified into 4 groups according to the presence of CKD and/or anemia on hospital admission (with CKD/with anemia n = 222, with CKD/without anemia n = 299, without CKD/with anemia n = 151, without CKD/without anemia n = 775). Angiographic acute results of primary PCI were similar among the 4 groups. The patients with CKD had a significantly higher in-hospital overall mortality rate than the patients without CKD, and in the presence or absence of CKD, patients with anemia tended to have a higher in-hospital mortality rate than the patients without anemia. According to a multivariate analysis, anemia on admission was found to be an independent predictor of in-hospital mortality, whereas admission CKD and admission eGFR were statistically not independent predictors. Moreover, the multivariable adjusted odds ratio of in-hospital death in AMI patients with CKD alone was 1.855 (95% CI 0.929-3.706), and that in AMI patients with CKD/with anemia was 3.384 (95% CI 1.697-6.748).These results suggest that among real-world, unselected Japanese AMI patients undergoing primary PCI, the combination of CKD and anemia on admission confers significant adverse effects on in-hospital mortality.

We performed comparative analyses of Legionella pneumophila serogroup (SG) 1 isolates obtained during 2005-2012 in Toyama Prefecture, Japan, by sequence-based typing (SBT) and pulsed-field gel electrophoresis (PFGE). Seventy-three isolates of L. pneumophila SG 1, including 17 isolates from patients, 51 from public baths, 4 from cooling towers, and 1 from a shower, were analyzed. The isolates were classified into 43 sequence types (STs) by SBT and 52 types by PFGE. Fourteen STs were unique to Toyama Prefecture, as determined from the SBT database of European Working Group for Legionella Infections (EWGLI), as of October 31, 2012. ST505 strain was identified in 4 isolates from patients and 5 isolates from public baths, and these isolates belonged to 2 PFGE types. These, however, were similar because of the difference with only two restriction fragments, indicating that ST505 strain was prevalent among L. pneumophila SG 1 isolates in this area. ST505 strains isolated from patients and public baths were distributed along the river in a western part of Toyama Prefecture. SBT and PFGE profiles of 3 clinical isolates were identical with those of 3 environmental isolates from the suspected origins of the infection in each case, respectively. This finding suggested that SBT and PFGE were useful for epidemiological study. Furthermore, by SBT analysis, we identified a clonal group formed only by 7 clinical isolates that are not associated with bathwater, suggesting that they were derived from unrecognized sources.

We investigated the prevalence of Legionella species isolated from puddles on asphalt roads. In addition, we carried out sequence-based typing (SBT) analysis on the genetic relationship between L. pneumophila serogroup 1 (SG 1) isolates from puddles and from stock strains previously obtained from sputum specimens and public baths. Sixty-nine water samples were collected from puddles on roads at 6 fixed locations. Legionella species were detected in 33 samples (47.8%) regardless of season. Among the 325 isolates from puddles, strains of L. pneumophila SG 1, a major causative agent of Legionnaires' disease, were the most frequently isolated (n = 62, 19.1%). Sixty-two isolates of L. pneumophila SG 1 from puddles were classified into 36 sequence types (STs) by SBT. ST120 and ST48 were identified as major STs. Environmental ST120 strains from puddles were found for the first time in this study. Among the 14 STs of the clinical isolates (n = 19), 4 STs (n = 6, 31.6%), including ST120, were also detected in isolates from puddles on roads, and the sources of infection in these cases remained unclear. The lag-1 gene, a tentative marker for clinical isolates, was prevalent in puddle isolates (61.3%). Our findings suggest that puddles on asphalt roads serve as potential reservoirs for L. pneumophila in the environment.

Data regarding relationship between pulse pressure (PP) at admission and in-hospital outcome in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are still lacking. A total of 1413 primary PCI-treated AMI patients were classified into quintiles based on admission PP (<40, n = 280; 40-48, n = 276; 49-57, n = 288; 58-70, n = 288; and ≥71 mmHg, n = 281). The patients with PP < 40 mmHg tended to have higher prevalence of male, smoking, and Killip class ≥3 at admission; right coronary artery, left main trunk (LMT), or multivessels as culprit lesions; larger number of diseased vessels; lower Thrombolysis in Myocardial Infarction (TIMI) grade in the infarct-related artery before/after primary PCI; and higher value of peak creatine phosphokinase concentration. Patients with PP < 40 mmHg had highest mortality, while patients with PP 49-57 mmHg had the lowest: 11.8 % (<40), 7.2 % (40-48), 2.8 % (49-57), 5.9 % (58-70), and 6.0 % (≥71 mmHg). On multivariate analysis, Killip class ≥3 at admission, LMT or multivessels as culprit lesions, chronic kidney disease, and age were the independent positive predictors of the in-hospital mortality, whereas admission PP 49-57 mmHg, hypercholesterolemia, and TIMI 3 flow before/after PCI were the negative ones, but admission PP < 40 mmHg was not. These results suggest that admission PP 49-57 mmHg might be correlated with better in-hospital prognosis in Japanese AMI patients undergoing primary PCI.

Background: The Japan Society of Diabetes Mellitus reported that the leading cause of death in patients with diabetes mellitus (DM) was chronic liver disease; however, there are limited studies investigating the cause of liver injury in these patients. Our study aimed to clarify the clinicopathological features of liver injury and the characteristics of nonalcoholic fatty liver disease (NAFLD) in DM patients., Methods: In total, 5,642 DM patients and 365 histologically proven NAFLD patients were enrolled. Clinical and laboratory parameters and liver biopsy results were, respectively, recorded and analyzed for the two sets of patients., Results: Positivity rates for Hepatitis B surface antigens (HBsAg) and anti-hepatitis C virus antibodies (anti-HCV Ab) were 1.7 and 5.1 %, respectively. The proportion of drinkers consuming 20-59 g and ≥60 g alcohol daily was 14.9 and 4.3 %, respectively. The percentage of DM patients with elevated serum alanine aminotransferase (ALT) levels (≥31 IU/L) was 28.6 %. Alcohol consumption had no significant effect on serum ALT levels. Seventy-two percent of HBsAg-positive patients were serum hepatitis B virus (HBV)-DNA negative, whereas 10 % exhibited high levels of the same (>4.0 log copies/ml). Thirty-eight percent of anti-HCV Ab-positive patients were serum HCV-RNA negative. Among the NAFLD patients, the frequencies of NASH and advanced stage NASH were significantly higher in male DM patients than in male patients without DM., Conclusions: Although HBsAg- and anti-HCV Ab-positivity rates were high in our Japanese DM patients, a majority of liver injuries could be associated with NAFLD/nonalcoholic steatohepatitis.

The aim of this study was to examine the link between Campylobacter jejuni isolates obtained from chicken meat (n = 7) and gastroenteritis patients (n = 744). In total, 751 isolates were subjected to Lior serotyping. All the isolates from chicken meats were serotyped as Lior serotype 76 (LIO76). Among 23 of the identified LIO76 strains, 13 strains (6 from chicken meat and 7 from clinical specimens) were indistinguishable by Penner serotyping, antimicrobial susceptibility testing, and pulsed-field gel electrophoresis. These strains were isolated in 2 different Japanese prefectures in 2004-2005, suggesting that chicken meat is an etiological agent of Campylobacter gastroenteritis and that a diffuse outbreak occurred during this time. Therefore, a continuous surveillance program should be established in Japan in order to prevent Campylobacter gastroenteritis, especially large-scale food-borne outbreaks.

Background: Nonalcoholic fatty liver disease (NAFLD) includes a broad range of liver pathologies from simple steatosis to cirrhosis and fibrosis, in which a subtype accompanying hepatocyte degeneration and fibrosis is classified as nonalcoholic steatohepatitis (NASH). NASH accounts for approximately 10-30% of NAFLD and causes a higher frequency of liver-related death, and its progression of NASH has been considered to be complex involving multiple genetic factors interacting with the environment and lifestyle., Principal Findings: To identify genetic factors related to NAFLD in the Japanese, we performed a genome-wide association study recruiting 529 histologically diagnosed NAFLD patients and 932 population controls. A significant association was observed for a cluster of SNPs in PNPLA3 on chromosome 22q13 with the strongest p-value of 1.4 × 10(-10) (OR = 1.66, 95%CI: 1.43-1.94) for rs738409. Rs738409 also showed the strongest association (p = 3.6 × 10(-6)) with the histological classifications proposed by Matteoni and colleagues based on the degree of inflammation, ballooning degeneration, fibrosis and Mallory-Denk body. In addition, there were marked differences in rs738409 genotype distributions between type4 subgroup corresponding to NASH and the other three subgroups (p = 4.8 × 10(-6), OR = 1.96, 95%CI: 1.47-2.62). Moreover, a subgroup analysis of NAFLD patients against controls showed a significant association of rs738409 with type4 (p = 1.7 × 10(-16), OR = 2.18, 95%CI: 1.81-2.63) whereas no association was obtained for type1 to type3 (p = 0.41). Rs738409 also showed strong associations with three clinical traits related to the prognosis of NAFLD, namely, levels of hyaluronic acid (p = 4.6 × 10(-4)), HbA1c (p = 0.0011) and iron deposition in the liver (p = 5.6 × 10(-4))., Conclusions: With these results we clearly demonstrated that Matteoni type4 NAFLD is both a genetically and clinically different subset from the other spectrums of the disease and that the PNPLA3 gene is strongly associated with the progression of NASH in Japanese population.

Background & Aims: Nonalcoholic steatohepatitis (NASH) can progress to hepatocellular carcinoma (HCC). We aimed to characterize the clinical features of NASH patients with HCC., Methods: In a cross-sectional multicenter study in Japan, we examined 87 patients (median age, 72 years; 62% male) with histologically proven NASH who developed HCC. The clinical data were collected at the time HCC was diagnosed., Results: Obesity (body mass index ≥25 kg/m(2)), diabetes, dyslipidemia, and hypertension were present in 54 (62%), 51 (59%), 24 (28%), and 47 (55%) patients, respectively. In nontumor liver tissues, the degree of fibrosis was stage 1 in 10 patients (11%), stage 2 in 15 (17%), stage 3 in 18 (21%), and stage 4 (ie, liver cirrhosis) in 44 (51%). The prevalence of cirrhosis was significantly lower among male patients (21 of 54, 39%) compared with female patients (23 of 33, 70%) (P = .008)., Conclusions: Most patients with NASH who develop HCC are men; the patients have high rates of obesity, diabetes, and hypertension. Male patients appear to develop HCC at a less advanced stage of liver fibrosis than female patients., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Group G Streptococcus strains isolated from patients with severe invasive infections in the period 2002-2008 were surveyed and their prevalence compared with that observed in the period 1995-2001 in Japan. Strains with genotypes stg485, stg6792, stc36, stg6, and stg652 were isolated in both periods, whereas various new genotypes appeared in 2002-2008 and some genotypes found in 1995-2001 were not found subsequently, thus indicating a change in the prevalent genotyped strains causing severe invasive streptococcal infections.

Objective: Detection of prostate cancer needs a biopsy of the prostate. Suspecting cancer from an increase in prostate-specific antigen (PSA) has a high negative rate at an initial prostate biopsy. Cases with negative initial biopsy may be the candidates of subsequent biopsy. For lowering unnecessary repeat biopsy, the use of predictive factors before a repeat biopsy is applied for indication., Methods: Seventy-seven cases with negative initial prostate biopsy received a repeat biopsy and factors for the detection of cancer were examined., Results: PSA doubling time distinguished a part of cancer cases. Its sensitivity of 30, 50 and 70 months was 36.6%, 30.4% and 10%, respectively. Cancer case did not show PSA doubling time of >100 months in general. Values of PSA transition zone density, %Free/total PSA and PSA velocity were similar between cancer and no cancer cases., Conclusions: PSA doubling time was one of the predictive factors for the detection of prostate cancer and was valuable for avoiding unnecessary repeat biopsy in some cases.

Background: Several clinical studies have demonstrated an inverse relationship between hospital volume of primary percutaneous coronary interventions (PCI) and in-hospital mortality. However, the relationships among hospital primary PCI volume, angiographic results, and in-hospital prognosis in patients with acute myocardial infarction (AMI) have not been fully investigated in Japan., Methods and Results: Using the AMI-Kyoto Multi-Center Risk Study database between January 2000 and December 2005, hospitals were classified into quintiles based on their annual volume of primary PCI. The fifth quintile of hospitals was labeled as high-volume, and the other quintiles were combined and defined as low-volume. Although patients undergoing primary PCI in high-volume hospitals (high-volume group, n=764) had a larger number of diseased vessels at initial coronary angiography and lower Thrombolysis In Myocardial Infarction (TIMI) flow grade in the infarct-related artery before PCI, compared with those in low-volume hospitals (low-volume group, n=1,021), the rates of achieving TIMI flow grade 3 just after PCI in the high-volume group was significantly higher than that in the low-volume group. The overall in-hospital mortality did not differ between the 2 groups. On multivariate analysis, in AMI patients undergoing primary PCI, Killip class >or=3 at admission, multivessel disease or left main trunk (LMT) as culprit lesion, number of diseased vessels >or=2 or diseased LMT, and age were the independent positive predictors of in-hospital mortality, whereas the TIMI flow grade 3 after primary PCI and elapsed time <24 h were the negative ones, but not low-volume hospital., Conclusions: Angiographic results of primary PCI in high-volume hospitals were superior to those in low-volume hospitals, but there was no significant difference in the in-hospital mortality between AMI patients in high-volume hospitals and those in low-volume hospitals.

Background: Obesity is an established risk factor for coronary heart disease. However, data on the relationship between obesity and prognosis following acute myocardial infarction (AMI) are still lacking in Japan., Methods and Results: In the present study, 1,458 AMI patients were enrolled in the AMI-Kyoto Multi-Center Risk Study between January 2000 and December 2003. Among survivors of hospitalized AMI, clinical characteristics and medium-term prognosis were retrospectively compared between 240 normal weight male patients [body mass index (BMI) 18.5-25.0 kg/m2, normal weight group], and 116 obese male patients (BMI > or = 25.0 kg/m2, obese group), who could be followed up after hospital discharge. The obese group were younger and had higher prevalence of smoking and hypercholesterolemia than the normal weight group. The two groups had similar angiographic findings and outcomes of primary percutaneous coronary intervention. During the follow-up period (mean 2.18 years for normal weight, 2.15 years for obese), overall mortality rate as well as event-free survival rate did not differ significantly between the two groups. Multivariate analysis showed the presence of previous myocardial infarction, diabetes mellitus, and age were predictors of medium-term mortality, but BMI was not., Conclusions: These results suggest that obesity is not associated with increased medium-term mortality and cardiac morbidity in Japanese male survivors hospitalized for AMI.

Background: Data on the medium- and long-term prognosis of young Japanese patients with acute myocardial infarction (AMI) are still lacking., Methods and Results: In the present study, 1,458 AMI patients were enrolled in the AMI-Kyoto Multi-Center Risk Study between January 2000 and December 2003. Of these, clinical characteristics and medium-term prognosis were retrospectively compared in 21 young patients < 40 years (young group), and 190 non-young patients 60-70 years old (non-young group) who could be followed after hospital discharge. The young group was all male and had higher prevalence of current smoking and greater body mass index, but previous myocardial infarction (MI) and hypertension were more prevalent in the non-young group. The young group had a higher prevalence of single-vessel disease and a lesser incidence of left circumflex coronary artery as the culprit lesion. The acquisition rates of Thrombolysis In Myocardial Infarction 3 flow after primary percutaneous coronary intervention did not differ between the 2 groups, but the data of maximal creatine kinase was significantly higher in the young group. During the follow-up period (average 2.42 years for young, 2.37 years for non-young), survival and event-free survival rates and incidence of major adverse cardiac events (MACE) did not differ between the 2 groups. The predictor of MACE during follow-up period was the presence of multivessel disease in the young group, whereas the presence of multivessel disease, history of previous MI and longer hospitalization were the predictors of MACE in the non-young group., Conclusions: These results suggest that the medium-term prognosis in young AMI patients is comparable to that of non-young AMI patients in Japan.

Background: The prevalence and clinical manifestations of acute myocardial infarction (AMI) in young patients in Japan have not been fully investigated., Methods and Results: In the present study, 1651 AMI patients were enrolled in the AMI-Kyoto Multi-Center Risk Study between January 2000 and June 2004. Of these, the clinical background, risk factors, angiographic findings, acute results of primary percutaneous coronary intervention (PCI) and in-hospital outcomes for 27 young patients <40 (young group), and 338 non-young patients 60

In a population endemic for HTLV-I and hepatitis C virus (HCV), HTLV-I infection has been associated with a suppressed cell-mediated immunity measured by anergy to purified protein derivative (PPD). However, the effect of HCV and the impact of coinfection with HTLV-I and HCV have not been previously evaluated. To approach this issue, PPD reactivity was analyzed among 300 study subjects in the community-based Miyazaki Cohort Study. An erythema of <10 mm in diameter 48 hours after subcutaneous injection of the antigen defined PPD anergy. Logistic regression was used to estimate the relative risks. With adjustment for age, gender, and HTLV-I seropositivity, anti-HCV positivity was not independently associated with PPD anergy (odds ratio [OR] = 1.1; 95% confidence interval [CI] = 0.6-1.9). Subjects with both anti-HCV and anti-HTLV-I had a fivefold risk of PPD anergy relative to those free of both infections (OR = 5.2; 95% CI = 1.9-13.8). The risk was nearly threefold among those with anti-HTLV alone (OR = 2.8; 95% CI = 1.4-5.3). Thus, coinfected study subjects were 1.9 times more likely to have PPD anergy compared with those singly infected with HTLV-I (p = .34). HCV infection may slightly increase the risk of PPD anergy among HTLV-I carriers.

To assess the relationship of anti-Tax antibody to human T-cell lymphotropic virus type-I (HTLV-I) transmission, the sero-prevalence of HTLV-I was analyzed among married couples and among mother/child (both adults) pairs. HTLV-I seroprevalence was significantly higher among wives with anti-Tax+ than those with anti-Tax- HTLV-I carrier husbands (82.4% vs. 59.5%). However, in the group of wives aged 60 years or older, there was no statistical difference in HTLV-I seropositivity based on the husbands' anti-Tax sero-status. In the group whose wives were less than 60 years old, more anti-Tax sero-positive than sero-negative husbands had high DNA levels (57.1% and 20.0%), whereas in the group of husbands whose wives were aged 60 years or older, the number of anti-Tax sero-positive and sero-negative individuals with high DNA levels was similar. HTLV-I sero-prevalence was significantly higher among the adult men with anti-Tax+ carrier mothers than those with anti-Tax- carrier mothers (52.0% vs. 14.3%). For women, HTLV-I sero-prevalence did not differ significantly according to their mothers' anti-Tax sero-status. Our results suggest that the presence of anti-Tax antibody in HTLV-I carriers is an age-dependent risk factor for male-to-female HTLV-I transmission. Furthermore, the effect of the mother's anti-Tax antibody as a risk factor for vertical HTLV-I transmission could be observed in men even after becoming adults.

We investigated the cervical level of carotid bifurcation, diameter of common carotid artery (CCA) and internal carotid artery (ICA) in 147 Japanese patients (150 arteries, range of age 31-79) and in 490 Hungarian patients (517 arteries, range of age 12-77). The cervical level of carotid bifurcation was determined by comparison with cervical vertebra. The carotid bifurcation of Japanese was most frequent at the lower part of 3rd cervical vertebra but in Hungarian the bifurcation was most frequent at the middle part of 4th cervical vertebra. Japanese carotid bifurcation was high-positioned compared with Hungarian. The mean CCA diameter in Japanese was 7.47 mm in male and 7.07 mm in female, in Hungarian 9.24 mm in male and 7.80 mm in female. The mean ICA diameter in Japanese was 4.96 mm in male and 4.83 mm in female, in Hungarian 8.56 mm in male and 7.66 mm in female. CCA and ICA diameter were larger in male than in female. The diameter of CCA had a significantly positive correlation with age (p < 0.002) but ICA had no similar correlation.