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Emission of ethylene from the needles of Japanese red pine, Pinus densiflora, was measured in air-polluted areas in Hiroshima, Japan. We applied a suitable protocol to determine the rate of ethylene emission from the excised needles. The influence of excision of needles on ethylene emission was not detected during the first 4 h of incubation at 20 deg. C. Ethylene emissions were low in the unpolluted (clean) areas regardless of the altitude or season. The emission of stress ethylene increased with the atmospheric NO2 concentration, suggesting that atmospheric NOx or related substances induced the higher ethylene emission in the polluted areas (near urban and industrial areas). In all cases, 1-year-old needles emitted significantly larger amounts of ethylene than the current needles. Ethylene emission did not increase evenly in the polluted areas, but the frequency of trees emitting high ethylene increased. Therefore, threshold rates for the baseline ethylene emission were proposed. [ABSTRACT FROM AUTHOR]

Background: An analysis was conducted in Japan to determine the most cost-effective neuraminidase inhibitor for the treatment of influenza virus infections from the healthcare payer's standpoint., Objective: This study reanalysed the findings of a previous study that had some limitations (no probabilistic sensitivity analysis and quality of life scores measured by the EQ-5D-3L instead of the EQ-5D-5L) and used a decision tree model with only three health conditions., Methods: This study incorporated new data from a network meta-analysis study into the first examination. The second examination involved constructing a new decision tree model encompassing seven health conditions and identifying costs, which consisted of medical costs and drug prices based on the 2020 version of the Japanese medical fee index. Effectiveness outcomes were measured using EQ-5D-5L questionnaires for adult patients with a history of influenza virus infections within a 14-day time horizon. Deterministic and probabilistic sensitivity analyses were performed to examine the uncertainty., Results: In the first examination, the base-case cost-effectiveness analysis confirmed that oseltamivir outperformed laninamivir, zanamivir and peramivir, making it the most cost-effective neuraminidase inhibitor. The second examination revealed that oseltamivir dominated the other agents. Both deterministic and probabilistic sensitivity analyses showed robust results that validated oseltamivir as the most cost effective among the four neuraminidase inhibitors., Conclusions: This study thus reaffirms oseltamivir's position as the most cost-effective neuraminidase inhibitor for the treatment of influenza virus infections in Japan from the perspective of healthcare payment. These findings can help decision makers and healthcare providers in Japan., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aim: Sodium-glucose cotransporter 2 (SGLT2) inhibitors often cause a transient decrease in glomerular filtration rate (GFR) shortly after the initiation, referred to as the 'initial drop'. However, the clinical significance of this initial drop in real-world practice remains unclear., Materials and Methods: Using the nationwide Japan Chronic Kidney Disease Database, we examined factors that affected the initial drop, in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). We also evaluated the effects of the initial drop on a composite kidney outcome (a decline in GFR of ≥50% or progression to end-stage kidney disease)., Results: Data from 2053 patients with CKD and T2DM newly prescribed an SGLT2 inhibitor were analysed. The follow-up period after SGLT2 inhibitor administration was 1015 days (interquartile range: 532, 1678). Multivariate linear regression models revealed that the concomitant use of the renin-angiotensin system inhibitors and diuretics, urinary protein levels ≥2+, and changes in GFR before the initiation of the SGLT2 inhibitor were associated with a larger initial GFR decline (β = -0.609, p = .039; β = -2.298, p < .001; β = -0.936, p = .048; β = -0.079, p < .001, respectively). Patients in the quartile with the largest initial GFR decline experienced a higher incidence of the subsequent composite kidney outcome than those in the other quartiles (p < .001)., Conclusions: The concomitant use of renin-angiotensin system inhibitors and diuretics, higher urine protein levels and pre-treatment GFR changes were associated with a larger initial GFR decline. Of these factors, the use of a diuretic had the largest effect. Furthermore, patients with CKD and T2DM experiencing an excessive initial GFR drop might be at a higher risk of adverse kidney outcomes., (© 2024 John Wiley & Sons Ltd.)

Background/aim: Organs of the digestive system are frequent sites of cancer development, and digestive tract cancers are the leading causes of death worldwide, including in Japan. Most of these cancers are associated with smoking or drinking habits. This study focused on the clinical and genomic characteristics of patients with these cancers using the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, which comprises a large volume of data on Japanese patients who have undergone tumor profiling gene panel tests., Patients and Methods: The genomic and clinical data from patients with digestive tract cancers registered in C-CAT between 2019 and 2023 were retrospectively reviewed. The data were derived from 412 patients with esophageal squamous cell carcinoma, 558 with gastric adenocarcinoma, 3,368 with colorectal adenocarcinoma, 139 with hepatocellular carcinoma, 2,050 with cholangiocarcinoma, and 2,552 with pancreatic ductal adenocarcinoma., Results: CDKN2A, CDKN2B, and MTAP mutations were associated with both smoking and drinking history, and patients with these mutations had a worse prognosis. Almost all gene alterations in CDKN2B and MTAP were deletions, often accompanied by CDKN2A deletion. CDKN2A mutation emerged as the most decisive prognostic factor among these mutations. Although CDKN2A mutations were frequently seen in esophageal squamous cell carcinoma, cholangiocarcinoma, and pancreatic ductal adenocarcinoma, statistically significant differences in survival outcomes were only identified in the latter two., Conclusion: CDKN2A mutations were associated with smoking and drinking in digestive cancers. This mutation was prevalent among patients with cholangiocarcinoma and pancreatic ductal adenocarcinoma, for whom they could serve as prognostic factors., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: It is well known that kidney injury is vital organ damage in Fabry disease (FD). Renin-angiotensin system (RAS) inhibitors are known to reduce proteinuria in patients with chronic kidney disease (CKD) by dilating the glomerular export arteries and reducing intraglomerular pressure. This improvement in intraglomerular pressure, although lowering the glomerular filtration rate, is thought to prevent renal damage and be renoprotective in the long term. RAS inhibitors may be effective in FD patients with proteinuria to prevent the progression of kidney disease, however, the degree to which they are used in clinical practice is unknown., Methods: The J-CKD-DB-Ex is a comprehensive multicenter database that automatically extracts medical data on CKD patients. J-CKD-DB-Ex contains data on 187,398 patients in five medical centers. FD patients were identified by ICD-10. Clinical data and prescriptions of FD patients between January 1 of 2014, and December 31 of 2020 were used for the analysis., Results: We identified 39 patients with FD from the J-CKD-DB-Ex including those with suspected FD. We confirmed 22 patients as FD. Half of the patients received RAS inhibitors. RAS inhibitors tended to be used in CKD patients with more severe renal impairment., Conclusions: This case series revealed the actual clinical practice of FD patients with CKD. In particular, we found cases in which patients had proteinuria, but were not treated with RAS inhibitors. The database was shown to be useful in assessing the clinical patterns of patients with rare diseases., (© 2023. The Author(s).)

Aim: Among patients with Immunoglobulin A (IgA) nephropathy, we aimed to identify trajectory patterns stratified by the magnitude of haematuria and proteinuria using repeated urine dipstick tests, and assess whether the trajectories were associated with kidney events., Methods: Using a nationwide multicentre chronic kidney disease (CKD) registry, we analysed data from 889 patients with IgA nephropathy (mean age 49.3 years). The primary outcome was a sustained reduction in eGFR of 50% or more from the index date and thereafter. During follow-up (median 49.0 months), we identified four trajectories (low-stable, moderate-decreasing, moderate-stable, and high-stable) in both urine dipstick haematuria and proteinuria measurements, respectively., Results: In haematuria trajectory analyses, compared to the low-stable group, the adjusted hazard ratios (HRs) (95% confidence interval [CI]) for kidney events were 2.59 (95% CI, 1.48-4.51) for the high-stable, 2.31 (95% CI, 1.19-4.50) for the moderate-stable, and 1.43 (95% CI, (0.72-2.82) for the moderate-decreasing groups, respectively. When each proteinuria trajectory group was subcategorized according to haematuria trajectories, the proteinuria group with high-stable and with modest-stable haematuria trajectories had approximately 2-times higher risk for eGFR reduction ≥50% compared to that with low-stable haematuria trajectory., Conclusion: Assessments of both haematuria and proteinuria trajectories using urine dipstick could identify high-risk IgA nephropathy patients., (© 2023 Asian Pacific Society of Nephrology.)

Adequate blood pressure (BP) management poses a significant challenge in improving the prognosis of patients undergoing dialysis. We aimed to investigate the relationship between pre-dialysis systolic blood pressure (SBP) and underlying disease in Japanese patients undergoing dialysis, based on prefectural location, and assess the association between pre-dialysis SBP and cardiovascular disease (CVD) mortality rate. We extracted the basic information of 336,182 patients who were undergoing dialysis in 2021 from the Web-based Analysis of Dialysis Data Archives database. Data on average pre-dialysis SBP were analyzed according to sex, prefectural location, and diabetic status, and the CVD mortality rate for each prefecture was calculated. The mean pre-dialysis SBP of the patients (males, 66.3%; mean age, 69.7 ± 12.5 years) was 151.9 ± 24.7 mmHg. Overall, 133,037 patients had underlying diabetic kidney disease (DKD). The patients with DKD were younger, had a shorter dialysis duration, and a higher pre-dialysis SBP than those with non-DKD comorbidities. The prefecture-based mean pre-dialysis SBP values were all higher than 140 mmHg. At the prefectural level, CVD mortality rate was positively correlated with pre-dialysis SBP (r = 0.3127, p = 0.0324) and diastolic blood pressure (r = 0.3378, p = 0.0202) among female patients. At the prefectural level, pre-dialysis SBP is >140 mmHg in Japanese patients undergoing dialysis, especially in those with DKD. The positive association between pre-dialysis SBP and CVD mortality rate suggests that optimal BP management at the prefectural level may reduce CVD mortality rates. At the prefectural level, pre-dialysis SBP is higher than 140 mmHg in Japanese patients undergoing dialysis, especially higher in those with DKD., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The prevalence of hypertension is high among patients undergoing dialysis. We extracted data of patients undergoing dialysis between 2012 and 2020 with recorded pre-dialysis systolic blood pressure (SBP) using a web-based national database in Japan. Following the 2019 Japanese Society of Hypertension guidelines, we classified SBP and assessed its trends over time based on sex, age, diabetes status, and the anti-hypertensive medication use. Using the 2020 database, we examined 336,759 Japanese patients undergoing dialysis (114,249 female; 222,510 male). The mean age was 69.4 ± 12.5 years, and the mean SBP was 152.3 ± 24.7 mm Hg. The prevalence rate of pre-dialysis hypertension was 70.2%, with 32.5%, 24.5%, and 13.2% of patients having grade I, grade II, and grade III hypertension, respectively. From 2014 to 2020, prevalence rate of pre-dialysis hypertension and absolute values of pre-dialysis SBP were higher in dialysis patients with diabetes than in those without diabetes across all age groups and sexes. Younger patients with diabetes or those on anti-hypertensive medication exhibited an SBP of approximately 160 mm Hg. Cerebrovascular death in patients with diabetes was associated with a higher rate of pre-dialysis hypertension than that in those without diabetes, and there was a significant difference in the prevalence of grade III hypertension between the two groups. In conclusion, the mean pre-dialysis SBP among patients undergoing dialysis remained high, and younger patients with diabetes or those receiving anti-hypertensive medications had poor blood pressure control. Optimal blood pressure management may be necessary to reduce the risk of cardiovascular mortality., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: Membranoproliferative glomerulonephritis (MPGN) is a rare glomerular injury that causes nephrotic syndrome and end-stage kidney disease. The nationwide demographics and treatment of Japanese patients with primary MPGN have not yet been reported., Methods: We collected clinical personal records of patients with primary MPGN between 2015 and 2018 from the national registry organized by the Japanese Ministry of Health, Labour, and Welfare and investigated the characteristics of primary MPGN throughout Japan., Results: Of 258 patients with primary MPGN, 199 and 59 showed nephrotic and non-nephrotic syndrome, respectively. The median age at onset was higher in patients with nephrotic syndrome than in those with non-nephrotic syndrome (45 [24-63] vs. 35 [14-53] years, respectively; P = 0.010). The use of oral prednisolone was significantly higher in patients with nephrotic syndrome than in those with non-nephrotic syndrome (73.9% vs. 59.3%, respectively; P = 0.032). When patients were divided into three age groups: adolescent and young adult group (≤ 39 years; n = 80), middle adult group (40-64 years; n = 111), and older adult group (≥ 65 years; n = 67), the use of oral prednisolone, cyclosporine, and mizoribine was significantly higher in the adolescent and young adult group than in the middle adult group. The mean dosage of oral prednisolone and mizoribine showed no differences among the three age groups., Conclusion: The national registry of clinical personal records of primary MPGN could provide an informative insight into the characteristics, clinical features, and treatment approaches for patients with primary MPGN in Japan., (© 2023. The Author(s).)

The nationwide clinical features of Japanese patients with primary nephrotic syndrome (NS), including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or membranous nephropathy (MN), have not yet been reported. We collected the clinical personal records of patients with primary NS between 2015 and 2018 from the national registry organized by the Japanese Ministry of Health, Labour, and Welfare. Overall, the demographics, chronic kidney disease classification based on glomerular filtration rate and albuminuria, and treatment of 6036 patients were collected: 3394 (56.2%) with MCD, 677 (11.2%) with FSGS, 1455 (24.1%) with MN, and 510 (8.5%) with others. MN patients were older than MCD and FSGS patients (67 vs. 42 and 47 years, respectively). Steroid-dependent NS or frequently relapsing NS was found in 70.2%, 40.5%, and 24.6%, whereas steroid-resistant NS was found in 6.4%, 36.0%, and 37.9% of patients in the MCD, FSGS, and MN, respectively. The present oral prednisolone use (mean dose, mg/day) was 87.2% (21.2), 80.9% (20.0), and 77.5% (18.8) of patients in the MCD, FSGS, and MN, respectively. The national registry of clinical personal records of primary NS could provide an informative insight into the characteristics, clinical features, and treatment approaches for patients with primary NS in Japan., (© 2023. Springer Nature Limited.)

The purpose of this study was to examine the usefulness of an online learning program, Learning Program for New Faculty Members, in conveying knowledge of educational practice to newly appointed nursing faculty members. The study participants were assistant professors and research associates from nursing programs in Japan, with less than 5 years of educational experience. In total, 99 people participated in this study, and data from 97 were analyzed. Participants in the control group (43) were frequency matched to those in the intervention group (54) for sex, age, final degree, clinical experience, and academic experience. A pre-test was conducted using an original questionnaire, and there were no significant differences between the two groups in knowledge about educational practice. The intervention group then participated in the Learning Program for New Faculty Members online, at their convenience. After the intervention, a post-test was conducted. In the intervention group, post-test scores were significantly higher for all items except Item 3 (Conducting Class). The intervention and control groups' post-test scores were 23.55 vs 16.90 for Item 1 (Student Understanding and Support), 28.20 vs 22.17 for Item 2 (Syllabus and Class Design) and 5.40 vs 2.97 for Item 4 (Understanding of Educational Theories). The Learning Program for New Faculty Members was therefore considered to be effective in helping newly appointed nursing faculty members to acquire knowledge. The program was able to overcome the time and environmental constraints of newly appointed nursing faculty members., Competing Interests: The authors have no conflicts of interest to declare.

Background: Fabry disease (FD) is an X-linked inherited disease where renal complications are associated with a poor prognosis. However, little is known about the prevalence of Fabry nephropathy (FN) in patients with chronic kidney disease (CKD). We extracted FN data from the Japan Renal Biopsy Registry, analyzed the prevalence of FN, and examined the correlation between clinical characteristics and renal involvement according to sex differences and hemi- and heterozygosity in patients with FD., Methods: A total of 38,351 participants who underwent renal biopsy were retrospectively enrolled, and FN was determined. The clinical characteristics of FD patients were examined based on sex differences., Results: Twenty-nine patients (0.076%) (19 males and 10 females, mean age: 43.7 ± 15.5 years old) were diagnosed with FN. Median estimated urinary protein (UP) and mean eGFR levels were 0.9 [interquartile range (IQR) [0.7-1.6] g/gCr and 67.1 ± 36.8 mL/min/1.73 m 2 , respectively. Mean systolic blood pressure (SBP) was 126.4 ± 17.1 mmHg and diastolic blood pressure was 76.1 ± 12.6 mmHg. An inverse correlation between eGFR and logarithm UP levels was observed (r 2  = 0.23, p = 0.02), SBP was positively associated with logarithm UP (r 2  = 0.34, p = 0.004) overall and inversely associated with eGFR (r 2  = 0.25, p = 0.007) regardless of sex, and SBP was an independent determinant of proteinuria (p = 0.004) and eGFR (p = 0.007)., Conclusions: The prevalence of biopsy-proven FN was 0.076%. Since SBP is associated with eGFR regardless of zygosity, strict SBP control might be necessary to prevent progression to end-stage kidney disease in both male and female patients with FN., (© 2022. The Author(s).)

Background: Recent clinical reports indicate a correlation between new-onset and relapse of nephrotic syndrome (NS) following coronavirus 2019 (COVID-19) vaccination in patients with glomerular diseases. However, there are no reports of a nationwide survey on NS following COVID-19 vaccination in Japan., Methods: We conducted a web-based survey of council members of the Japanese Society of Nephrology (581 members, 382 facilities) to elucidate the relationship between COVID-19 vaccination and new-onset and relapse of NS., Results: Following COVID-19 vaccination, 27 patients (male: 15, 55.6%) with new-onset (n = 6) and relapse (n = 21) of NS were reported. Of them, 12 (44.4%) patients were diagnosed with minimal change disease at the occurrence of NS. Five patients developed a slight increase in serum creatinine levels; however, none progressed to severe renal dysfunction., Conclusion: Our findings clarify the clinical features of new-onset and relapse of NS following COVID-19 vaccination. Although there was no obvious progression to severe renal dysfunction, clinicians and pathologists should be aware that NS is a potential adverse effect of the vaccines., (© 2022. The Author(s).)

Background: The prognosis of lupus nephritis (LN) has improved following the introduction of effective immunosuppressive therapy and progress in supportive care. This study examined recent renal and patient prognosis for adults with LN in Japan., Methods: We conducted a nationwide retrospective cohort study of LN patients who received a renal biopsy between 2007 and 2012 that were registered in the Japan Renal Biopsy Registry. Of 623 registered adults with LN from 25 institutions and their affiliated or community hospitals, 489 were eligible for this study., Results: The median age at renal biopsy was 39 years, and 82.2% of patients were female. Renal biopsies were performed in 348 patients with new-onset LN, 106 with relapse LN, and 35 with refractory LN. The distribution of ISN/RPS 2003 Classes was as follows: I 1.6%; II 5.3%; III (± V) 27.0%; IV (± V) 47.0%; V 18.4%; VI 0.6%. During the median observation period of 63.8 months, 36 patients (7.3%) reached a doubling of serum creatinine or end-stage kidney disease (ESKD), and 28 patients (5.7%) died. The 5 year renal and patient survival rates were 93.9% and 94.7%, respectively. Multivariate analysis revealed body mass index (BMI) and estimated glomerular filtration rate (eGFR) were independent risk factors for a doubling of serum creatinine in ESKD. Age and eGFR were independent risk factors for death., Conclusion: Recent prognosis for adults with LN are relatively good in Japan. Risk factors for impaired renal function are BMI and eGFR at renal biopsy, while age and eGFR are risk factors for death., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Objective: Randomized controlled trials have shown kidney-protective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy, as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitor initiation modify treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients, is unknown., Research Design and Methods: Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease., Results: At baseline, mean age at initiation of the SGLT2 inhibitor ( n = 1,033) or other glucose-lowering drug ( n = 1,033) was 64.4 years, mean eGFR was 68.1 mL/min per 1.73 m 2 , and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs. other drugs 0.75 mL/min/1.73 m 2 per year [0.51 to 1.00]). During a mean follow-up of 24 months, 103 composite kidney outcomes occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26-0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiation of SGLT2 inhibitors ( P heterogeneity ≥ 0.35)., Conclusions: The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria., (© 2021 by the American Diabetes Association.)

The reclassification of membranoproliferative glomerulonephritis (MPGN) into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G) based on immunofluorescence findings in kidney biopsies has provided insights into these two distinct diseases. C3G is further classified into dense deposit disease and C3 glomerulonephritis (C3GN) based on electron micrographic findings. Although these diseases have poor outcomes, limited Japanese literature confined to small, single-center cohorts exist on these diseases. We retrospectively analyzed 81 patients with MPGN type I and III from 15 hospitals in the Japan Renal Biopsy Registry to compare demographic, clinical characteristics and treatment outcomes of patients with IC-MPGN to those with C3GN. Of the 81 patients reviewed by immunofluorescence findings in kidney biopsies, 67 patients had IC-MPGN and 14 patients had C3GN. Age at diagnosis and systolic and diastolic pressure were higher and proteinuria and impaired renal function were significantly more prevalent in patients with IC-MPGN than those with C3GN. About 80% of the patients in both groups were treated with immunosuppressive therapy. At last follow-up (median 4.8 years), complete remission rate of proteinuria was significantly higher in patients with C3GN (64.3%) than in those with IC-MPGN (29.9%; P = 0.015). The renal survival rate was lower in patients with IC-MPGN when compared to C3GN (73.1% vs. 100%; log-rank, P = 0.031). Systolic blood pressure and renal function at baseline were independent predictors of progression to end-stage kidney disease. The overall prognosis of patients with C3GN is more favorable than for patients with IC-MPGN., Competing Interests: The authors have declared that no competing interests exist.

Objective Fabry disease (FD) is a hereditary lysosomal storage disease that has been highlighted as a possible etiology of stroke at a young age and presents with other various neurological symptoms. Since FD is rare, limited information is currently available on the prevalence of neurological symptoms in Japanese patients with FD. Therefore, we examined the characteristics of neurological symptoms and brain magnetic resonance imaging (MRI) findings in adult Japanese patients with FD. Methods This was a retrospective, single-center study. We reviewed neurological symptoms and brain MRI findings in the medical records of 12 adult Japanese patients with FD diagnosed by a gene analysis of the α-galactosidase gene. Results Ten out of 12 patients with FD presented with the following neurological symptoms: acroparesthesia (n=6), headache (n=5) [migraine (n=4)], hypohidrosis (n=5), and cerebral infarction (n=3). Two and three of the patients with migraine were complicated by ischemic stroke and coronary spastic angina, respectively. Five and 10 patients presented with periventricular hyperintensity and deep white matter hyperintensity, respectively, on brain MRI. Two out of eight patients had cerebral microbleeds. Seven out of 11 patients had a dilated basilar artery diameter on magnetic resonance angiography. There were no patients with the pulvinar hyperintensity sign. Conclusion Patients with FD present with various neurological symptoms. Headache, particularly migraine, might be a major neurological symptom in patients with FD. Since migraine, ischemic stroke, and coronary spastic angina might occur together in FD, caution is needed when administering triptan to FD patients with migraine.

Background: Pharmacoeconomic studies have been less performed in Japan. The objective of this study was to clarify which neuraminidase inhibitor (NI; oseltamivir, zanamivir, laninamivir, and peramivir) is most cost-effective in an adult outpatient setting in Japan., Objective: To clarify which neuraminidase inhibitor (NI; oseltamivir, zanamivir, laninamivir, and peramivir) is most cost-effective in an adult outpatient setting in Japan., Methods: Cost-effectiveness analysis was constructed from the healthcare payer's perspective. A decision tree model was constructed with probabilities from relevant randomized controlled trials. Costs included medical costs and drug prices. Medical costs were obtained from the medical fee schedule table (2016 version). We also applied authorized medication costs. Outcomes of effectiveness were measured using EQ-5D-3L questionnaires for adult patients who had experienced influenza virus infections previously. Time horizon was 14 days in this study., Results: Cost-effectiveness ratios for oseltamivir, zanamivir, laninamivir, and peramivir were 393 674 Yen/quality-adjusted life year (QALY; US$3883.41/QALY), 408 241 (US$4027.10), 407 980 (US$4024.53), and 444 264 (US$4382.45), respectively. The cost-effectiveness analysis base-case analysis revealed oseltamivir as the most cost-effective NI. Zanamivir was dominated. Incremental cost effectiveness ratio (ICER) for laninamivir and peramivir were 1 129 459 Yen/QALY (US$11 141.58/QALY) and 1 287 118 (US$12 696.81), respectively. One-way sensitivity analyses revealed that minimum ICERs for laninamivir based on "quality of life (QOL) values (95% confidence interval)" was -596 850 Yen/QALY (US-$5887.64/QALY) owing to high cost and less effective. Also, maximum ICER for peramivir based on"QOL values" was 14 717 518 Yen/QALY (US$145 181.32/QALY); a value more than the 5 000 000 Yen/QALY threshold., Conclusions: The study results reveal oseltamivir as the most cost-effective NI for the treatment of influenza virus infection in an adult outpatient setting. Our findings may provide decision makers with scientific evidence for clinical and economic evaluation to achieve optimal therapeutic outcomes., (Copyright © 2020. Published by Elsevier Inc.)

Background: The Japan Chronic Kidney Disease Database (J-CKD-DB) is a nationwide clinical database of patients with chronic kidney disease (CKD) based on electronic health records. The objective of this study was to assess the prevalences of hyperuricemia and electrolyte abnormalities in Japanese patients with CKD., Methods: In total, 35,508 adult outpatients with estimated glomerular filtration rates of 5-60 ml/min/1.73 m2 in seven university hospitals were included this analysis. The proportions of patients with CKD stages G3b, G4, and G5 were 23.5%, 7.6%, and 3.1%, respectively., Results: Logistic regression analysis showed that prevalence of hyperuricemia was associated with CKD stages G3b (adjusted odds ratio [95% confidence interval]: 2.12 [1.90-2.37]), G4 (4.57 [3.92-5.32]), and G5 (2.25 [1.80-2.80]). The respective prevalences of hyponatremia, hypercalcemia, hyperphosphatemia, and narrower difference between serum sodium and chloride concentrations were elevated in patients with CKD stages G3b, G4, and G5, compared with those prevalences in patients with CKD stage G3a. The prevalences of hyperkalemia were 8.3% and 11.6% in patients with CKD stages G4 and G5, respectively. In patients with CKD stage G5, the proportions of patients with optimal ranges of serum uric acid, potassium, corrected calcium, and phosphate were 49.6%, 73.5%, 81.9%, and 56.1%, respectively., Conclusions: We determined the prevalences of hyperuricemia and electrolyte abnormalities in Japanese patients with CKD using data from a nationwide cohort study., Competing Interests: The authors have no conflicts of interest to declare.

Unattended automated office blood pressure (AOBP) measurement has been endorsed as the preferred in-office measurement modality in recent Canadian and American clinical practice guidelines. However, the difference between AOBP and conventional office blood pressure (CBP) under the environment of a health checkup remains unclear. We aimed to identify the clinical significance of AOBP as compared to CBP under the environment of a health checkup. There were 491 participants (333 females, mean age of 62.5 years) who were at least 20 years old, including 179 participants who were previously diagnosed with hypertension. Mean AOBPs were 131.8 ± 20.9/76.6 ± 11.7 mm Hg, and CBPs were 135.6 ± 21.6/77.3 ± 11.5 mm Hg. There was a difference of 3.9 mm Hg in systolic blood pressure (SBP) and 0.8 mm Hg in diastolic BP between AOBP and CBP. In all participants, SBP and pulse pressure, as well as the white coat effect (WCE), increased with age. The cutoff value used was 140/90 mm Hg for CBP and 135/85 mm Hg for AOBP, and the prevalence of WCE and masked hypertension effect (MHE) was 12.4% and 14.1%, respectively. Even in a health checkup environment of the general population, there was a difference between the AOBP and CBP, and the WCE was observed more strongly in the elderly with a history of hypertension, suggesting that a combination of AOBP with CBP may be useful in detecting WCE and MHE in all clinical scenarios including health checkups, and help solve the "hypertension paradox" not only in Japan but in all over the world., (© 2020 Wiley Periodicals LLC.)

Background: The Japan Chronic Kidney Disease Database (J-CKD-DB) is a nationwide clinical database of patients with chronic kidney disease (CKD) based on electronic health records. The objective of this study was to assess the prevalence of anemia and the utilization rate of erythropoiesis-stimulating agents (ESAs) in Japanese patients with CKD., Methods: In total, 31,082 adult outpatients with estimated glomerular filtration rates of 5-60 ml/min/1.73 m2 in seven university hospitals were included this analysis. The proportions of patients with CKD stages G3b, G4, and G5 were 23.5%, 7.6%, and 3.1%, respectively., Results: The mean (standard deviation) hemoglobin level of male patients was 13.6 (1.9) g/dl, which was significantly higher than the mean hemoglobin level of female patients (12.4 (1.6) g/dl). The mean (standard deviation) hemoglobin levels were 11.4 (2.1) g/dl in patients with CKD stage G4 and 11.2 (1.8) g/dl in patients with CKD stage G5. The prevalences of anemia were 40.1% in patients with CKD stage G4 and 60.3% in patients with CKD stage G5. Logistic regression analysis showed that diagnoses of CKD stage G3b (adjusted odds ratio [95% confidence interval]: 2.32 [2.09-2.58]), G4 (5.50 [4.80-6.31]), and G5 (9.75 [8.13-11.7]) were associated with increased prevalence of anemia. The utilization rates of ESAs were 7.9% in patients with CKD stage G4 and 22.4% in patients with CKD stage G5., Conclusions: We determined the prevalence of anemia and utilization rate of ESAs in Japanese patients with CKD using data from a nationwide cohort study., Competing Interests: The authors have declared that no competing interests exist.

Background: The frequency and prognosis of resected deficient mismatch repair (dMMR) pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study was designed to assess the frequency of dMMR and its clinicopathological relevance in Japanese patients with PDAC treated with surgical resection., Methods: A total of 400 consecutive patients with PDAC who underwent surgical resection at Hiroshima University were enrolled. Immunohistochemical staining with four antibodies including MLH1, MSH2, MSH6, and PMS2 was used to determine the presence of dMMR in PDAC specimens. Statistical analyses were applied to evaluate the frequency and clinical outcomes of these patients., Results: Of these 400 patients, five (1.3%) had dMMR (two had MLH1 deficiency, two had PMS2 deficiency, and one had MSH2 deficiency). We found a significantly different histological differentiation pattern between patients with dMMR and those with proficient mismatch repair (pMMR) (P = .03). Univariate survival analysis revealed no significant differences between dMMR and pMMR in recurrence-free survival (P = .268) or overall survival (P = .173)., Conclusions: The incidence of dMMR in Japanese patients with resected PDAC is low, and we found no ethnic-specific differences when comparing the incidence to that in Caucasian patients. In the current study, no significant difference was found in recurrence-free and overall survival between patients with dMMR and pMMR., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

A 79-year-old man presented to our hospital with 1-month history of discomfort on swallowing and pain in the thoracodorsal region. Image investigation revealed a tumor lesion affecting the area from the lower esophagus to the gastric antrum, and small cell carcinoma of esophagus was diagnosed based on biopsy. He was treated with resection of the lower esophagus and the upper part of the stomach and a postoperative chemoradiotherapy. The patient follow-upwas without recurrence until a malignant lymphoma developed 4 years and 5 months after the surgery. Chemotherapy was provided for the malignant lymphoma, however, the patient died 6 years and 4 months after the surgery for small cell carcinoma of esophagus. Small cell endocrine carcinoma of the esophagus is a relatively rare disease and its prognosis is poor. In our patient, long-term survival was achieved with multimodal treatment, however malignant lymphoma developed during the follow-upp eriod. This is the second case of metachronous cancer after the treatment for small cell carcinoma of the esophagus in Japan, and it is considered to be extremely rare.

The purpose of this study is to understand the reading habits of Japanese pharmacists regarding clinical trial literature in 2014. Questionnaires were mailed to 1997 pharmacists in Miyagi Prefecture. Six hundreds and five [342 (56.5%) hospital pharmacists and 254 (42.0%) community pharmacists] responded to questionnaires (Response rate: 30.3%). Regarding the question, "Do you habitually read clinical trial literature?", 19.5% of hospital and 8.3% community pharmacists responded "yes", respectively, which showed both pharmacists are not habitual readers of clinical trial literature. That would be because they did not study critical reading of clinical trial literature at pharmacy schools as well as their work environments to access and retrieve clinical trial literature were limited.

Background and Purpose: Fall-induced injuries and resulting deaths are a serious health problem among older adults. The most common risk factors for falls in older adults are muscle weakness, gait deficiencies, and balance deficits. Patients with end-stage hip osteoarthritis (OA) also have many hip dysfunctions, and these all have the potential to increase the risk of falls. However, the incidence and risk factors for falls in patients with end-stage hip OA remain unclear. The aim of this study was to determine the incidence of falls in women with end-stage hip OA and to identify risk factors for falls in this patient population., Methods: This study was a cross-sectional analysis. One hundred fifty-three women with end-stage hip OA (mean age = 64.0 years) and 112 age-matched healthy women (mean age = 64.1 years) were analyzed using available data. All participants were examined for the number and circumstances of falls in the past year. The circumstances of falls included the location, time, direction, cause, and injury. We examined the outcome of hip function, ambulatory ability, physical activity, and limping severity in women with end-stage hip OA. Multivariate logistic regression analysis was used to identify factors influencing falls in women with hip OA., Results: The incidence of at least 1 fall in the past year was significantly higher in women with end-stage hip OA (30.1%) than in healthy women (12.5%) (P < .001). Falls in women with end-stage hip OA were most often caused by tripping and falling forward during the daytime. The majority of falls (65.2%) resulted in injuries and 13.0% resulted in fractures. The occurrence of a fall significantly correlated with limping (odds ratio = 3.26, 95% confidence interval = 1.49-7.14, P = .003) and knee extensor muscle strength (odds ratio = 0.22, 95% confidence interval = 0.05-0.85, P = .029)., Conclusions: Women with end-stage hip OA have an increased risk of falls and fall-induced injuries. The prevention of falls in this vulnerable population should be a priority among health care practitioners. In particular, women who are limping and have reduced lower knee extensor strength should take care to avoid falls.

Purpose of Review: To estimate the impact of the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines for high blood pressure (BP) on the next hypertension guidelines in Asia., Recent Findings: The 2017 ACC/AHA guidelines for high BP in adults changed the diagnostic threshold and the management goal of BP from 140/90 to 130/80 mmHg. Another characteristic of the new guideline is its focus on a practical approach for the effective management of hypertension by using home and ambulatory BP monitoring; this point is also recommended in the 2014 Japanese Society of Hypertension Guidelines for the Management of Hypertension. In Japan, the guidelines for hypertension management are currently under revision and will be released in the spring of 2019. The core concept of the 2019 Japanese Society of Hypertension Guidelines for the Management of Hypertension, i.e., early and tight BP control over 24 h, will contribute to target-organ protection and cardiovascular disease prevention for Asians.

Objective: Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare autosomal recessive primary immunodeficiency. Hypogammaglobulinemia is a major manifestation of ICF syndrome, but immunoglobulin replacement therapy does not seem to be effective for some ICF patients. Therefore, we aimed to reassess the immunological characteristics of this syndrome., Methods: Eleven Japanese patients with ICF syndrome were enrolled. We performed whole-exome sequencing in four cases and homozygosity mapping using SNP analysis in two. We evaluated their clinical manifestations and immunological status., Results: We newly diagnosed six ICF patients who had tentatively been diagnosed with common variable immunodeficiency. We identified two novel mutations in the DNMT3B gene and one novel mutation in the ZBTB24 gene. All patients showed low serum IgG and/or IgG 2 levels and were treated by periodic immunoglobulin replacement therapy. Three of the six patients showed worse results of the mitogen-induced lymphocyte proliferation test. Analyses of lymphocyte subpopulations revealed that CD19 + CD27 + memory B cells were low in seven of nine patients, CD3 + T cells were low in three patients, CD4/8 ratio was inverted in five patients, CD31 + recent thymic emigrant cells were low in two patients, and CD19 + B cells were low in four patients compared with those in the normal controls. ICF2 patients showed lower proportions of CD19 + B cells and CD16 + 56 + NK cells and significantly higher proportions of CD3 + T cells than ICF1 patients. T cell receptor excision circles were undetectable in two patients. Despite being treated by immunoglobulin replacement therapy, three patients died of influenza virus, fatal viral infection with persistent Epstein-Barr virus infection, or JC virus infection. One of three dead patients showed normal intelligence with mild facial anomaly. Two patients presented with autoimmune or inflammatory manifestations. Infectious episodes decreased in three patients who were started on trimethoprim-sulfamethoxazole and/or antifungal drugs in addition to immunoglobulin replacement therapy. These patients might have suffered from T cell immunodeficiency., Conclusion: These results indicate that patients with ICF syndrome have a phenotype of combined immunodeficiency. Thus, to achieve a better prognosis, these patients should be treated as having combined immunodeficiency in addition to receiving immunoglobulin replacement therapy.

Background: The incidence and age distribution of membranoproliferative glomerulonephritis (MPGN) vary throughout the world by race and ethnicity. We sought to evaluate the clinical features, pathogenesis, and age distribution of MPGN among a large nationwide data from the Japan Renal Biopsy Registry (J-RBR)., Methods: A cross-sectional survey of 593 patients with MPGN (types I and III) registered in the J-RBR between 2007 and 2015 was conducted. Clinical parameters, and laboratory findings at diagnosis were compared between children (< 20 years), adults (20-64 years), and elderly patients (≥ 65 years)., Results: The median age of the patients was 59.0 years and mean proteinuria was 3.7 g/day. The rate of nephrotic syndrome was significantly higher in adults (40.4%) and elderly patients (54.0%) than in children (14.9%), whereas the rate of chronic glomerulonephritis was significantly higher in children (66.2%) than in adults (34.4%) and elderly patients (31.2%). According to the CGA risk classification, high-risk (red zone) cases accounted for 3.4% of children, 52.5% of adults and 84.1% of elderly patients with MPGN. As for pathogenesis, primary MPGN was most frequent (56.0%). Lupus nephritis was the most common disease among adult patients with secondary MPGN, whereas infectious disease was more common in elderly patients. Multiple regression analysis revealed that high systolic blood pressure and high proteinuria were independent factors associated with decreased estimated glomerular filtration rate (eGFR) in adults and elderly patients with MPGN., Conclusions: In Japan, adults and elderly patients with MPGN had a lower eGFR and severer proteinuria than children.

Background: We investigated the incidence and circumstances related to falls in patients before and after total hip arthroplasty (THA), and compared them with those in an age-matched control group., Methods: This is a prospective cohort study. A total of 140 women with severe hip osteoarthritis (OA) who underwent THA (OA group) and a control cohort of 319 age-matched healthy women were analyzed. We investigated the incidence and circumstances of falls before THA and during the first year after surgery. We assessed the Harris Hip Score and investigated hip pain and ambulatory ability using a self-administered questionnaire., Results: The incidence of at least one fall during the first year after THA in the OA group (30.0%) was significantly higher than that in the control group (13.5%) (P < .001), as were the rates of indoor falls (50.0%) and falls during daytime (66.2%). Although the incidence of fall-induced injuries after THA (37.8%) was significantly lower than that in the control group (62.5%), 5.9% of patients who experienced a fall developed a fracture. No significant differences were found in the number and circumstances of falls before and after THA, with 31.4% and 30.0% of the OA group reporting at least one fall in the 12 months before and after surgery, respectively. Self-reported pain, ambulation, and Harris Hip Score significantly improved after THA., Conclusion: Women undergoing THA have an increased risk of falls during the first year after surgery. Clinicians should suggest preventive measures during rehabilitation to prevent falling in post-THA women., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: This study aimed to examine the relationship between pedometer-assessed daily step count and all-cause mortality in a sample of elderly Japanese people., Methods: Participants included 419 (228 males and 191 females) physically independent, community-dwelling 71-year-old Japanese people. The number of steps per day was measured by a waist-mounted pedometer for seven consecutive days at baseline. Participants were divided into quartiles based on their average number of steps/day (first quartile, < 4503 steps/day; second quartile, 4503-6110 steps/day; third quartile, 6111-7971 steps/day; fourth quartile, > 7972 steps/day) and were followed up over a mean period of 9.8 years (1999-2010) for mortality., Results: Seventy-six participants (18.1%) died during the follow-up period. The hazard ratios (adjusted for sex, body mass index, cigarette smoking, alcohol intake, and medication use) for mortality across the quartiles of daily step count (lowest to highest) were 1.00 (reference), 0.81 (95%CI, 0.43-1.54), 1.26 (95%CI, 0.70-2.26), and 0.46 (95%CI, 0.22-0.96) (P for trend = 0.149). Participants in the highest quartile had a significantly lower risk of death compared with participants in the lowest quartile., Conclusion: This study suggested that a high daily step count is associated with a lower risk of all-cause mortality in physically independent Japanese elderly people.

Background: Pancreatectomy, including pancreatoduodenectomy and distal pancreatectomy, often causes postoperative pancreatic exocrine insufficiency (PEI). Our aim was to clarify a relationship between remnant pancreatic volume and postoperative PEI., Methods: A total of 227 patients who underwent pancreatoduodenectomy or distal pancreatectomy were enrolled in this study. All patients underwent a (13)C-labeled mixed triglyceride breath test to assess pancreatic exocrine function and abdominal dynamic computed tomography for assessing remnant pancreatic volume after pancreatectomy at a median of 7 months postoperatively. The percent (13)CO2 cumulative dose at 7 hours (% dose (13)C cum 7 h) < 5% on the (13)C-labeled mixed triglyceride breath test was considered diagnostic of postoperative PEI. Relationships between postoperative PEI and clinicopathologic factors including remnant pancreatic volume were analyzed., Results: Pancreatoduodenectomy and distal pancreatectomy were performed in 174 (76.7%) and 53 (23.3%) patients, respectively. Of the 227 patients, 128 (56.3%) developed postoperative PEI. Postoperative % dose (13)C cum 7 h was strongly correlated with remnant pancreatic volume (r = .509, P < .001). The cut-off value of remnant pancreatic volume for predicting postoperative PEI was 24.1 mL by receiver operating characteristic curve analysis. Multivariate analysis revealed that remnant pancreatic volume < 24.1 mL was the only independent predictive factor for the development of postoperative PEI in patients who underwent pancreatectomy (P < .001, hazard ratio; 5.94, 95% confidence interval; 2.96-12.3)., Conclusion: Remnant pancreatic volume is associated closely with postoperative PEI after pancreatectomy. Remnant pancreatic volume may predict postoperative PEI in patients who undergo pancreatectomy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: There have been few reports on falls in patients who have undergone total hip arthroplasty (THA). In the present study, we aimed to investigate the incidence and circumstances of falls in post-THA patients and to identify the factors associated with falling., Materials and Methods: After excluding comorbidities, osteoarthritis without THA, and patients who had undergone THA within the previous 1 year, 214 patients [11 males, 203 females; mean (SD) age, 66.0 (8.7) years] living independently for at least 1 year after THA were analyzed as available data. Using a self-administered questionnaire, we investigated the number and circumstances of falls in the preceding year, as well as functional outcome and ambulatory ability via the Oxford Hip Score. Multivariate logistic regression analysis was used to identify factors influencing falls in post-THA patients., Results: The incidence of at least one fall in the past year was 36 %. Falls were most often caused by tripping and falling forward during the daytime. In the present study, 37.7 % of falls resulted in injuries and 5.2 % resulted in fractures. Experience of fall was significantly related to medication [odds ratio (OR) 4.09, 95 % confidence interval (CI) 1.90-8.80, P < 0.001] and postoperative duration (OR 0.89, 95 % CI 0.81-0.98, P < 0.05)., Conclusions: Thus, patients have an increased risk for falls and fall-induced injuries after THA. Falls in post-THA patients are associated with medication and shorter postoperative duration. Therefore, it is essential to prevent falls in patients who have undergone THA, particularly during the early postoperative period and among patients administered medications.

Metabolic syndrome confers an increased risk of cardiovascular disease (CVD) in the general population. The relationship between adiponectins, and clinical outcomes in patients undergoing hemodialysis remains controversial. We investigated whether adiponectins, biomarkers of inflammation, nutrition status and clinical features predict the mortality of patients undergoing hemodialysis for 6 years. We measured baseline plasma total and high-molecular-weight (HMW) adiponectins, tumor necrosis factor (TNF)-α, serum high sensitivity C-reactive protein (hsCRP), and clinical characteristics including visceral fat area (VFA) and the Geriatric Nutritional Risk Index (GNRI) in 133 patients undergoing chronic hemodialysis. Forty-one of the 133 patients died during follow-up. The deceased patients were significantly older, had more prior CVD and diabetes, higher TNF-α and hsCRP levels but lower GNRI. VFA, and total and HMW adiponectin did not significantly differ between the two groups. TNF-α and hsCRP levels and GNRI score were significant for predicting all-cause and cardiovascular mortality in receiver operating curve analyses. When stratified by a GNRI score of 96, Cox proportional hazards analyses identified TNF-α as a significant predictor of all-cause mortality (hazard ratio [HR] 1.23; P = 0.038) and hsCRP as a significant predictor of all-cause and cardiovascular mortality (HR, 2.32, P = 0.003; HR 2.30, P = 0.012, respectively) after adjusting for age, sex, diabetes mellitus, and prior CVD, only in malnourished patients. These results demonstrate that malnutrition and the inflammatory markers TNF-α and hsCRP, but not metabolic markers, including VFA and adiponectins have a significant impact on 6-year all-cause and cardiovascular mortality in Japanese patients undergoing hemodialysis., (© 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.)

Background: The study aim was to determine the short- and long-term results of lateral pancreaticojejunostomy for chronic pancreatitis at a single center in Japan., Methods: The records of 64 consecutive patients were retrospectively reviewed. All patients underwent surgery at Hiroshima University Hospital between December 1996 and April 2013. Long-term follow-up was performed in 58 patients (91%) for a median period of 34 months., Results: The 53 men (83%) and 11 women (17%) had a mean age of 55 years. The etiology of pancreatitis was chronic alcohol abuse in 44 patients (69%). The major indication for surgery was acute pancreatitis exacerbation (80%). There was no postoperative mortality. Postoperative morbidity occurred in 21 patients (33%), with severe complications requiring non-surgical intervention in four (6%). The percentage of pain-free patients after surgery was 91%, and further acute exacerbation was prevented in 95%. Four patients (7%) required subsequent surgery for pancreatitis-related complications. Of the patients that completed follow-up, 33 (57%) had diabetes mellitus, including 11 patients (19%) with new-onset diabetes; 30 patients (56%) developed pancreatic exocrine insufficiency., Conclusions: Full-length lateral pancreaticojejunostomy is safe, feasible, and effective for managing chronic pancreatitis. The technique prevents further exacerbations and maintains appropriate pancreatic endocrine and exocrine function., (© 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background and Objectives: Data regarding renal disease in the elderly (age ≥65 years old) and very elderly (age ≥80 years old) Japanese are extremely limited. The aim of this study was to examine the causes of renal disease and their clinical presentations in elderly patients who underwent renal biopsy., Design, Setting, Participants, and Measurements: From July 2007 to November 2011, all of the elderly native renal biopsy patients who had been registered in the Japan Renal Biopsy Registry (J-RBR; 2802 including 1596 males and 1206 females) were identified. Their data were compared with a control group of 7416 patients who ranged in age from 20 to 64 years old and were registered on the J-RBR over the same period. In addition, the clinical and pathological classifications of 276 very elderly patients were also analyzed., Results: The indications for biopsy were nephrotic syndrome (NS) in 36.2 and 50.7 % of the elderly and the very elderly patients, chronic nephritic syndrome in 31.8 and 17.4 %, and acute kidney injury including rapidly progressive glomerulonephritis in 18.6 and 22.5 %, respectively. Primary glomerular disease was the most frequent diagnosis, followed by MPO-ANCA-positive nephritis, IgA nephropathy (IgAN), and diabetic nephropathy. In primary GN including IgAN, membranous nephropathy (MN) was the most frequent histological type, followed by IgAN and minor glomerular abnormalities. A comparison with the control group showed that MN, MPO-ANCA-positive nephritis, and amyloid nephropathy were more common in the elderly (P < 0.001), and IgAN was less common (P < 0.001). As for nephrotic syndrome in the elderly, MN was the most common histological type, followed by minimal change NS, diabetic nephropathy, amyloid nephropathy, and focal segmental glomerulosclerosis. There was a significant discrepancy between the urinary protein/creatinine ratio and daily proteinuria after the 7th decade of life., Conclusions: Renal biopsy is a valuable diagnostic tool, even in elderly and very elderly Japanese patients. In the future, modified clinical guidelines for elderly renal disease should be developed.

Background and Objectives: This study evaluated long-term outcomes for patients who received adjuvant gemcitabine plus S-1 chemotherapy after resection for pancreatic carcinoma., Methods: Seventy patients who underwent surgical resection of pancreatic carcinoma were enrolled prospectively into this study. All patients received adjuvant chemotherapy with 10 cycles of gemcitabine plus S-1 every 2 weeks. Each cycle consisted of intravenous gemcitabine 700 mg/m(2) on day 1 and oral S-1 50 mg/m(2) for seven consecutive days, followed by a 1-week pause of chemotherapy. Long-term survival results of adjuvant gemcitabine plus S-1 chemotherapy were analyzed for this cohort., Results: Median follow-up time was 51.2 months. Sixty percent of patients had node-positive disease and 79% of patients underwent R0 resection. Fifty-six patients (80%) completed adjuvant chemotherapy. Median overall and disease-free survival times were 35.4 and 23.8 months, respectively. Actuarial overall and disease-free survival rates were 89% and 64% at 1 year, 64% and 50% at 2 years, and 33% and 33% at 5 years, respectively. Only negative lymph node metastasis (P = 0.010) independently correlated with long-term survival by multivariate analysis., Conclusions: Long-term results of adjuvant gemcitabine plus S-1 chemotherapy suggest this regimen may be safe and promising as treatment for this patient population., (Copyright © 2012 Wiley Periodicals, Inc.)

Background and Aims: Poor physical performance is known to be inversely related to mortality. The purpose of the present study was to determine whether an association between physical performance and 10-year mortality could be extended to a Japanese 70-year-old community-dwelling population, and to compare findings with those found in an octogenarian population., Methods: Seventy-year-old subjects residing in Niigata city, Japan, participated. Baseline examinations, including a physical performance test of four tests of muscle strength, one test of balance, and one test of agility, were carried out in June 1998 for 600 participants, and these individuals were then followed for 10 years., Results: During the 10-year follow up, 80 subjects died. Cox regression analysis with adjustment for confounding factors showed that high scores in muscle strength tests for lower extremities, such as single-leg and double-leg extensor strength and isokinetic leg extensor power, were found to be related to decreases in total cause mortality., Conclusions: In an elderly 70-year-old Japanese community-dwelling population, poor muscle strength was found to be an independent predictor of total mortality. Together with our previous findings in an 80-year-old population, the association between poor strength and high mortality may have effects at 70 but not 80 years of age.

Objective: Patients with chronic kidney disease (CKD) are at a high risk for cardiovascular diseases including stroke. However, the characteristics of the stroke subtypes in patients with CKD remain to be determined., Methods: We investigated the associations between stroke subtypes and estimated glomerular filtration rate (eGFR), and traditional risk factors in 451 (males, 239; mean age, 71.1 y) acute stroke patients at our hospital between 2006 and 2010., Results: The stroke subtype was cardiogenic cerebral embolism in 129 (29%), cerebral hemorrhage in 104 (23%), unclassified cerebral infarction in 65 (14%), lacunar infarction in 65 (14%), subarachnoid hemorrhage in 41 (9%), atherothrombosis in 30 (7%), and transient ischemic attacks in 17 (4%). Among the 451 patients, 134 (30%) had CKD with eGFR <60 mL/min/1.73 m 2 . Compared with a group without CKD, mean age (75.9 vs. 69.0 years, p<0.05), the prevalence of atrial fibrillation (AF) (44% vs. 21%, p<0.01) and a history of cardiovascular disease (37% vs. 19%, p<0.01) were significantly higher in that with CKD. A comparison of stroke subtypes revealed a significantly higher incidence of cardiogenic cerebral embolism (36% vs. 26%, p<0.05) in the group with, than without CKD., Conclusion: We showed the prevalence of CKD in about 30% of acute stroke patients, and those patients were older, had a significantly higher prevalence of AF and a higher rate of cardiogenic cerebral embolism compared with patients without CKD. Thus, strict control of blood pressure and management of AF should be important to prevent stroke among patients with CKD.

The aim of this study was to clarify the relationship between dental occlusion and physical fitness by a longitudinal survey. A sample of 348 subjects (171 men and 177 women) aged 71 was investigated by Eichner index (EI) as an occlusal condition (Class A: no loss; Class B: partial loss; Class C: complete loss) and five types of physical fitness tests and were re-examined 8 years later. The upper 50% were sampled to analyze the correlation between each physical fitness decline and the EI at the baseline by logistic regression models. Logistic regression analyses revealed that leg extensor power (Class B vs. Class A; odds ratio=OR=4.61, p=0.010) and one-leg standing time with eyes open (Class C vs. Class A; OR=4.27, p=0.031) showed significant correlations with the EI at the baseline. In this study, partial or complete loss of occlusion was associated with a decline in leg extensor power or a decrease in one-leg standing time with eyes open. These findings suggest that maintenance of dental occlusion may prevent a decrease in activities of daily living in the elderly., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Fabry disease is an X-linked lysosomal storage disorder caused by mutations of the α-galactosidase A gene (GLA), and the disease is a relatively prevalent cause of left ventricular hypertrophy mimicking idiopathic hypertrophic cardiomyopathy. We assessed clinically 5 patients of a three-generation family and also searched for GLA mutations in 10 family members. The proband had left ventricular hypertrophy with localized thinning in the basal posterior wall and late gadolinium enhancement (LGE) in the near-circumferential wall in cardiovascular magnetic resonance images and her sister had vasospastic angina pectoris without organic stenosis of the coronary arteries. LGE notably appeared in parallel with decreased α-galactosidase A activity and increased NT-pro BNP in our patients. We detected a new GLA missense mutation (G195V) in exon 4, resulting in a glycine-to-valine substitution. Of the 10 family members, 5 family members each were positive and negative for this mutation. These new data extend our clinical and molecular knowledge of GLA gene mutations and confirm that a novel missense mutation in the GLA gene is important not only for a precise diagnosis of heterozygous status, but also for confirming relatives who are negative for this mutation.

In the 2004-2005 season, there was a large epidemic of the influenza B virus Yamagata group in Kobe, Japan. In hemagglutination inhibition tests, most of the clinical isolates from Kobe showed antigenicities similar to those of previous isolates (the vaccine-type virus). Only a few antigenic variants were isolated around the peak of the epidemic; however, Kobe residents developed antibodies against the variants during the season. The antigenic variants showed a one-point mutation of a nucleotide in the HA1 gene (C440A or G421A), which resulted in the substitution of one amino acid in the 150 loop of the HA molecule (T147N or G141R). The 150 loop is one of four epitopes of the hemagglutinin molecule of the influenza B virus. We established a system to detect one-point differences in the nucleotides of the 150 loop by means of high-resolution melting curve analysis with LCGreen. With this system, the isolates were determined to be the vaccine-type virus, antigenic variants, or a mixture of both. Some isolates were shown to be mixtures although they had been recognized as the vaccine-type virus with the hemagglutination inhibition tests. Thus, the antigenic variants appeared in the early period of the epidemic and were cocirculating with the vaccine-type virus during the epidemic.

Objective: The efficacy and safety of two types of phoshodiestrase type 5 ( PDE 5) inhibitors (sildenafil (sil) and vardenafil (var)) were investigated for multi-centric study., Subjects and Methods: One hundred and twenty five patients (55.9 +/- 10.9 years old) with erectile dysfunction (ED) were treated by both of sil and var. The patients were administered a pair of 25 mg of sil and 5 mg of var, or 50 mg of sil and 10 mg of var. The efficacy for ED and safety of these 2 drugs were evaluated after administration of each drugs at least 2 times., Results: The results showed that the score of international index of erectile function 5 (IIEF5) were elevated from 8.87 +/- 4.10 to 17.24 +/- 6.17 after treatments (p< 0.0001, Student' s t test). The efficacy rates for ED were 81.6% in sil and 81.6% in var, respectively. The adverse reactions rates such as headache, burning, palpitation, etc. were 13.6% in sil and 5.6% in var, which is significantly higher in sil (p = 0.032; chi2 test). These side effects were not serious at all, and there were no cases that gave up to use PDE5 inhibitors because of adverse reactions. According to individual patients experiences, 40.7% of patients preferred sil, 45.4% choose var. In addition, associated effects for quality of life (QOL) of ED patients treated by PDE5 inhibitors were analyzed. The results revealed that encouraging in life 46.5%, rejuvenation feeling 45.1%, self care for their health 28.2%, improvement of depression 12.7%, improvement of voiding dysfunction 5.6%, intimacy with partner 38.0%, good conversation with partner 18.3%, and so on., Conclusion: The treatments of ED by sil and var were very effective and safety. Furthermore, associated effects for QOL of ED patients were also improved with these treatments.

Background: The turning point in the deterioration of physical function seems to occur between the ages of 70 and 80 years. In particular, muscle strength may decline even more in subjects older than 75. A recent study found that the angiotensin-converting enzyme (ACE) genotype also affects physiological left ventricular hypertrophy. A very limited number of papers have examined genetic differences in resistance and endurance forms of a single sporting discipline., Objective: The purpose of this study was to evaluate the relationship between ACE genotype and physical function by controlling the known confounding factors including dental status., Methods: We selected 431 subjects who were aged 76 years and did not require special care for their daily activities. We conducted a medical examination, followed by 5 physical function tests, as follows: (1) maximum hand grip strength, (2) maximal isometric knee extensor strength, (3) maximal stepping rate for 10 s, (4) one-leg standing time with eyes open and (5) 10-meter maximum walking speed. Subjects were genotyped for the ACE intron 16 Alu insertion. In addition, serum concentrations of total cholesterol, total protein, IgA and IgG were measured at a commercial laboratory. The Eichner index was used as an indicator of occlusal condition. Multiple linear regression analysis was performed to evaluate the relationship between the ACE gene insertion/deletion (I/D) polymorphism and physical function considering confounding factors., Results: The ACE gene I/D polymorphism was positively associated with hand grip strength and 10-meter maximum walking speed. Betas of hand grip strength were 0.09 for I/D (p = 0.022) and 0.12 for insertion/insertion (I/I; p = 0.004). Betas of 10-meter walking speed were -0.11 for I/D (p = 0.093) and -0.14 for I/I (p = 0.039). Dental status such as Eichner index class C was significantly associated with one-leg standing time with eyes open (beta -0.11; p = 0.028)., Conclusion: This study suggests that there is a significant relationship between ACE genotype and physical function. In particular, subjects with the ACE deletion/deletion genotype were associated with upper extremities., (Copyright 2009 S. Karger AG, Basel.)

Monoclonal antibody 9B2 possesses hemagglutination inhibition activity against all the 2002/2003 influenza B virus Victoria group isolates in Kobe, Japan, as well as representative strains isolated between 1987 and 1997. The 9B2 epitope localizes three-dimensionally in the vicinity of antigenic site A of the hemagglutinin molecule, and amino acid substitutions in this region affected the binding of 9B2.

Sustainable sanitation is an approach for more ecological and sustainable water resources management. In this paper, we proposed one of the new integrated waste treatment systems: an "sustainable sanitation system" that includes separation of the black water from water system by a non-flushing toilet (bio-toilet), and a gray water treatment based on a biological and ecological concept. Sustainable sanitation system also converts the domestic waste to soil conditioners and fertilizers, for farmland use. As one of the case studies, Environmentally Symbiotic Housing in which people actually live using the bio-toilet for the black water treatment and the household wastewater treatment facility for the gray water was introduced. The availability of this system was investigated by analyzing the sawdust used in the bio-toilet and the quality of the effluent in the household wastewater treatment facility. As the result, the water content of the sawdust did not exceed 60% in any of the sampling points and the BOD and COD of the effluent of the household wastewater treatment facility were below 10 and 20 mg/L respectively, due to the low loading. Compared to the pollution load on the water environment created by the conventional system, it was found that the effluent of the house has a lower load than the tertiary treatment and the volume of the water consumption is 75% of the conventional system.

Purpose: This study was designed to analyze complications and prognosis for different types of stroke patients registered in Aichi Prefecture between 1993 and 2000., Methods: A total of 23,979 out of 27,304 registered patients in the Aichi stroke patient registration program with 4 type of strokes (cerebral thrombosis (CRT), cerebral embolism (CRE), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH)) were analyzed for complications and prognosis (survival, disability, dementia), with reference to gender, age-groups, and types of stroke., Results: A total of 13,365 (55.7%) male (65.5 +/- 12.2 yr: Mean +/- SD) and 10,614 (44.3%) female (69.7 +/- 13.3 yr) patients were registered. As the type of stroke, CRT comprised the highest percentage, both in males (49.5%) and females (41.1%), followed by ICH (males: 30.4%, females: 29.8%). The percentage of SAH in females (17.3%) was found to be about twice as high as that in males (8.3%). Analyses of complications revealed hypertension to be the greatest risk factor in both sexes (about 50%), followed by history of stroke (males: 20.1%, females: 16.2%). Male patients had a significantly higher overall survival rate (84.7%) than females (81.0%) (P <0.001). SAH was associated with the lowest survival rate in both sexes (about 60%), with statistical significance (P<0.001). Development of disability or/and dementia as sequela of stroke was higher in females (disability: 54.5%, dementia: 21.1%) than in males (44.2%, 15.1%, respectively) (P< 0.001). Logistic regression analyses revealed that the factors most contributing to death were advanced age, a history of stroke, heart disease, and renal insufficiency. For the development of disability and dementia, being femal, of advanced age, with a history of stroke, heart disease, and renal insufficiency were important. Abnormal lipid metabolism appeared to be a protection factor regarding prognosis (survival, disability, dementia)., Conclusions: This study demonstrated that hypertension is the most frequently reported complication for all types of stroke except CRE, and logistic regression analyses revealed that the factor contributing most to prognosis (survival, disability, dementia) was a history of stroke. The results suggested the importance of: i) removing hypertansion as the most significant risk factor, as well as diabetes and heart disease in order to prevent strokes; and ii) preventing re-attack(s) of stroke in order to improve the prognosis.