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1.
Targeting cholesterol biosynthesis for AT/RT: comprehensive expression analysis and validation in newly established AT/RT cell line.
Matsumoto, F, Yokogami, K, Yamada, A, Moritake, H, Watanabe, T, Yamashita, S, Sato, Y, Takeshima, H
Human cell. 2024;(2):523-530
Abstract
Atypical teratoid/rhabdoid (AT/RT) is a rare and highly malignant tumor of the central nervous system (CNS). It is most commonly found in children less than 5 years of age and is associated with inactivation of loss of function of SMARCB1/INI1. An experimental model for AT/RT is necessary to develop new and effective therapies. We established a patient-derived new cell line (MZ611ATRT), which showed loss of BAF-47. MZ611ATRT genetically features somatic heterozygous deletion of SMARCB1 and single nucleotide deletion of the residual allele, exon 5 ([c.541delC]), resulting in a stop codon at codon 954 by frameshift. We assessed the RNA-sequencing data of the other two AT/RT cell lines with forced expression of SMARCB1 available from public databases. We found SMARCB1 overexpression significantly down-regulates the expression of a group of enzymes related to cholesterol biosynthesis. Simvastatin was highly sensitive against MZ611ATRT cells and induced apoptosis (IC50 was 3.098 µM for MZ611ATRT, 41.88uM for U-87 MG, 23.34uM for IOMM-Lee, and 18.12uM for U-251 MG.). Pathways involved in cholesterol biosynthesis may be new targets for adjuvant therapy of AT/RT.
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2.
Calcium-Phosphorus Product Is Associated with Adverse Prognosis in Hospitalized Patients with Heart Failure and Chronic Kidney Disease.
Abe, S, Yoshihisa, A, Oohara, H, Sugawara, Y, Sato, Y, Misaka, T, Sato, T, Oikawa, M, Kobayashi, A, Yamaki, T, et al
International heart journal. 2024;(1):84-93
Abstract
It has been reported that high levels of calcium-phosphorus (Ca-P) product are an indicator of coronary calcification and mortality risk in patients undergoing chronic hemodialysis. In the present study, we aimed to evaluate the significance of Ca-P product to predict the prognosis of patients with heart failure (HF) and chronic kidney disease (CKD). We conducted a prospective observational study of 793 patients with decompensated HF and CKD, and measured the value of Ca-P product. The cut-off value was obtained from the survival classification and regression tree (CART) analysis to predict post-discharge all-cause mortality and/or worsening HF, and the patients were divided into 2 groups: a high group (Ca-P product > 28, n = 594) and a low group (Ca-P product ≤ 28, n = 199). We compared the patient baseline characteristics and post-discharge prognosis between the 2 groups. The age as well as the prevalence of male sex, ischemic etiology, and anemia were significantly higher in the low group than in the high group. In contrast, there was no difference in echocardiographic parameters between the 2 groups. In the Kaplan-Meier analysis (mean follow-up 1089 days), all-cause mortality and/or worsening HF event rates were higher in the low group than in the high group (log-rank P = 0.001). In the multivariable Cox proportional hazard analysis, lower Ca-P product was found to be an independent predictor of all-cause mortality and/or worsening HF (hazard ratio 0.981, P = 0.031). Lower Ca-P product predicts adverse prognosis in patients with HF and CKD.
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3.
Relationship between nutritional status and clinical outcomes among older individuals using long-term care services: A systematic review and meta-analysis.
Ogawa, M, Okamura, M, Inoue, T, Sato, Y, Momosaki, R, Maeda, K
Clinical nutrition ESPEN. 2024;:365-377
Abstract
BACKGROUND & AIMS Nutritional status is a significant issue in an aging society; however, the impact of the nutritional status of older individuals using long-term care services on the caregiving burden remains unclear. This systematic review and meta-analysis aimed to investigate the impact of nutritional issues on adverse outcomes in older individuals using long-term care services. METHODS We used data from the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Web of Science, CINAHL, and Ichu-shi Web databases. Original articles published in English or Japanese between January 2000 and July 2022 were included. The inclusion criteria were interventional and observational studies on individuals using long-term care services with aged ≥65 years and a focus on body weight or weight loss. Data on adverse outcomes related to caregiving burden, including the number of people requiring care, mortality, complications, activities of daily living (ADL), and quality of life, were collected. RESULTS The literature search yielded 7873 studies, of which 35 were ultimately included. Seven observational studies investigated mortality outcomes, and seven examined ADL outcomes. The meta-analysis revealed significantly higher mortality rates in individuals classified as underweight (BMI <18.5 kg/m2) than in those with BMI ≥18.5 kg/m2 (risk ratio [RR] 1.49; 95 % confidence interval [CI] 1.31 to 1.73, 0.22; I2 93 %). Further, on categorising the participants based on a BMI cutoff of 25 kg/m2, those with a BMI of <25 kg/m2 had a significantly increased mortality rate (RR 1.21; 95 % CI 1.04-1.40; I2 = 98 %). BMI and weight loss did not affect ADL. CONCLUSIONS Our findings indicate that underweight and weight loss are significantly associated with increased mortality in older individuals using long-term care services. Therefore, appropriate weight management is recommended for this population. However, further research is necessary owing to the high heterogeneity observed in this study.
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4.
Validation of Dietary Intake Estimated by Web-Based Dietary Assessment Methods and Usability Using Dietary Records or 24-h Dietary Recalls: A Scoping Review.
Murai, U, Tajima, R, Matsumoto, M, Sato, Y, Horie, S, Fujiwara, A, Koshida, E, Okada, E, Sumikura, T, Yokoyama, T, et al
Nutrients. 2023;(8)
Abstract
The goal was to summarize studies comparing the accuracy of web-based dietary assessments with those of conventional face-to-face or paper-based assessments using 24-h dietary recall or dietary record methods in the general population. Using two databases, mean differences and correlation coefficients (CCs) for intakes of energy, macronutrients, sodium, vegetables, and fruits were extracted from each study independently by the authors. We also collected information regarding usability from articles reporting this. From 17 articles included in this review, the mean dietary intake differences in the web-based dietary assessment compared to conventional methods, were -11.5-16.1% for energy, -12.1-14.9% for protein, -16.7-17.6% for fat, -10.8-8.0% for carbohydrates, -11.2-9.6% for sodium, -27.4-3.9% for vegetables, and -5.1-47.6% for fruits. The CC was 0.17-0.88 for energy, protein, fat, carbohydrates, and sodium, and 0.23-0.85 for vegetables and fruits. In three out of four studies reporting usability, more than half of the participants preferred the web-based dietary assessment. In conclusion, % difference and CC of dietary intake were acceptable in both web-based dietary records and 24-h dietary recalls. The findings from this review highlight the possibility of wide-spread application of the web-based dietary assessment in the future.
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Effect of aqueous olanexidine versus alcohol-based chlorhexidine for surgical skin antisepsis on incidence of surgical site infections in gastrointestinal surgery: multicentre randomised controlled clinical trial (OEDO trial) protocol.
Takeuchi, M, Obara, H, Furube, T, Kawakubo, H, Kitago, M, Okabayashi, K, Aoyama, J, Amemiya, R, Fujisaki, H, Sano, J, et al
BMJ open. 2023;(8):e074169
Abstract
INTRODUCTION Surgical site infections (SSIs) are among the most common nosocomial infections in surgery patients. Two types of preparations, povidone-iodine and chlorhexidine-alcohol, are commonly used in preoperative antiseptic procedures worldwide. However, there are inconsistencies among international guideline recommendations concerning skin antiseptics. This trial aimed to evaluate the superiority of olanexidine, which reduced SSI rates more than povidone-iodine in our previous randomised trial, over chlorhexidine-alcohol in clean-contaminated surgery. METHODS AND ANALYSIS This multicentre randomised controlled clinical trial will compare two antiseptics (1.5% olanexidine and 1.0% chlorhexidine-alcohol) to prevent SSI in clean-contaminated gastrointestinal surgeries with surgical wounds. On providing consent, patients aged <18 years will be included. The primary outcome will be the postoperative 30-day overall SSI rate, while the secondary outcomes will be the postoperative 30-day superficial incisional SSI rate, deep incisional SSI rate, organ/space SSI rate, positive bacterial wound culture rate, cultured bacterial strains, rates of intervention-related toxicity and allergic events (eg, erythema, pruritus, dermatitis and other symptoms of allergy around the region disinfected by the antiseptic during surgery), rate of reoperations due to SSI, medical economic effect indicators (based on health insurance claims) and hospital duration. The Mantel-Haenszel method will be used to estimate the adjusted risk ratio and its 95% CI for the primary analysis, which will compare the treatment effects. ETHICS AND DISSEMINATION The protocol was approved by the Institutional Review Board of Keio University School of Medicine and subsequently by the board of each participating site. Participant recruitment began in January 2023. The final results will be published in medical journals after international peer review. TRIAL REGISTRATION NUMBER UMIN000049712.
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6.
Controlling nutritional status score during hospitalization as a predictor of clinical outcome in patients with aneurysmal subarachnoid hemorrhage.
Shimizu, S, Hanai, T, Egashira, Y, Sato, Y, Sekiya, K, Nishida, S, Ishihara, M, Ishihara, T, Asada, R, Kobayashi, R, et al
Scientific reports. 2023;(1):12758
Abstract
Aneurysmal subarachnoid hemorrhage (aSAH) is a serious condition with high mortality and a high permanent disability rate. In this study, we examined the association of clinical outcome with the Controlling Nutritional Status (CONUT) score during hospitalization in aSAH patients. A single-center, retrospective observational study was conducted at Gifu University Hospital. Patients transported to the emergency room for aSAH and diagnosed with World Federation of Neurosurgical Societies (WFNS) grade III and IV aSAH between April 2004 and March 2021 were enrolled. A logistic regression model was constructed to evaluate the association of the CONUT score with a modified Rankin scale (mRS) ≥ 3 and delayed cerebral ischemia (DCI). 127 patients diagnosed with WFNS grade III and IV aSAH were analyzed. CONUT score was significantly associated with mRS ≥ 3 during hospitalization. The score obtained by subtracting the CONUT score at admission from the maximum CONUT score was significantly associated with mRS ≥ 3 at discharge. Moreover, the score obtained by subtracting the CONUT score at admission from the maximum CONUT score during the first 14 days was significantly associated with DCI within 14 days from admission. These findings indicate that CONUT score during hospitalization may be a useful daily marker for predicting poor outcomes in aSAH patients.
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Developing Multidisciplinary Management of Heart Failure in the Super-Aging Society of Japan.
Sato, Y, Kuragaichi, T, Nakayama, H, Hotta, K, Nishimoto, Y, Kato, T, Taniguchi, R, Washida, K
Circulation journal : official journal of the Japanese Circulation Society. 2023;(1):2-9
Abstract
The Japanese population is rapidly aging because of its long life expectancy and low birth rate; additionally, the number of patients with heart failure (HF) is increasing to the extent that HF is now considered a pandemic. According to a recent HF registry study, Japanese patients with HF have both medical and care-related problems. Although hospitalization is used to provide medical services, and institutionalization is used to provide care for frail older adults, it can be difficult to distinguish between them. In this context, multidisciplinary management of HF has become increasingly important in preventing hospital readmissions and maintaining a patient's quality of life. Academia has promoted an increase in the number of certified HF nurses and educators. Researchers have issued numerous guidelines or statements on topics such as cardiac rehabilitation, nutrition, and palliative care, in addition to the diagnosis and treatment of acute and chronic HF. Moreover, the Japanese government has created incentives through various medical and long-term care systems adjustments to increase collaboration between these two fields. This review summarizes current epidemiological registries that focus not only on medical but also care-related problems and the 10 years of multidisciplinary management experience in Japanese medical and long-term care systems.
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8.
Phase I Study of the Liposomal Formulation of Eribulin (E7389-LF): Results from the Advanced Gastric Cancer Expansion Cohort.
Shitara, K, Hirao, M, Iwasa, S, Oshima, T, Komatsu, Y, Kawazoe, A, Sato, Y, Hamakawa, T, Yonemori, K, Machida, N, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2023;(8):1460-1467
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Abstract
PURPOSE In the dose-expansion part of this open-label, phase I study, we explored the efficacy and safety of E7389-LF (liposomal formulation of eribulin) in Japanese patients with advanced gastric cancer. PATIENTS AND METHODS Patients with advanced gastric cancer who had been previously treated with ≥2 lines of chemotherapy received E7389-LF 2.0 mg/m2 every 3 weeks (the previously determined maximum tolerated dose, the primary objective of Study 114). Secondary objectives included objective response rate (ORR), progression-free survival (PFS), and safety; exploratory objectives included disease control rate (DCR) and clinical benefit rate (CBR), as well as pharmacodynamic measurements of serum biomarkers. RESULTS As of June 24, 2021, 34 patients were enrolled and treated (10 from the original dose-expansion cohort, expanded to include 24 additional patients). Six patients had partial responses, for an ORR of 17.6% [95% confidence interval (CI), 6.8-34.5], and the median PFS was 3.7 months (95% CI, 2.7-4.8). The DCR was 79.4% (95% CI, 62.1-91.3), and the CBR was 32.4% (95% CI, 17.4-50.5). Overall, 32 patients (94.1%) experienced treatment-related adverse events, and 26 patients (76.5%) experienced grade ≥3 events, most commonly neutropenia (41.2%) and leukopenia (29.4%). Of the 8 endothelial cell/vasculature markers tested in this study, 7 were significantly increased among patients treated with E7389-LF; these changes were generally consistent regardless of best overall response. CONCLUSIONS E7389-LF 2.0 mg/m2 every 3 weeks was tolerable and showed preliminary activity for the treatment of patients with gastric cancer.
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Change in phase angle is associated with improvement in activities of daily living and muscle function in patients with acute stroke.
Sato, Y, Yoshimura, Y, Abe, T, Nagano, F, Matsumoto, A, Wakabayashi, H
European geriatric medicine. 2023;(6):1333-1341
Abstract
PURPOSE The phase angle (PhA) is a simple index that reflects nutritional status and muscle quality. This study aimed to investigate the association between PhA changes and activities of daily living (ADL), muscle strength, and muscle mass in patients with acute stroke. METHODS This retrospective, observational, cross-sectional study included patients hospitalized for acute stroke. The primary outcome was functional independence measure (FIM) of motor gain. The secondary outcomes were changes in handgrip strength and skeletal muscle mass index (SMI) during hospitalization. Multivariate analysis was used to examine whether PhA changes were associated with outcomes, after adjusting for potential confounders. RESULTS Hundred and sixty one subjects (mean age 74.6 years, 92 men) were included in the study. Multivariate analysis showed that PhA change was significantly and positively correlated with the gain in FIM motor scores, both for men (β = 0.634, p < 0.001) and women (β = 0.660, p < 0.001). Furthermore, there were significant associations between PhA change and changes in handgrip strength for men (β = 0.222, p = 0.030) and women (β = 0.491, p < 0.001), as well as SMI for men (β = 0.556, p < 0.001) and women (β = 0.290, p = 0.025). CONCLUSIONS An increased phase angle was positively associated with ADL, muscle strength, and muscle mass at discharge in patients with acute stroke.
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Rationale and study design of the GOREISAN for heart failure (GOREISAN-HF) trial: A randomized clinical trial.
Yaku, H, Kato, T, Morimoto, T, Kaneda, K, Nishikawa, R, Kitai, T, Inuzuka, Y, Tamaki, Y, Yamazaki, T, Kitamura, J, et al
American heart journal. 2023;:18-25
Abstract
BACKGROUND The decongestion strategy using loop diuretics is essential for improving signs and symptoms of heart failure (HF). However, chronic use of loop diuretics in HF has been linked to worsening renal function and adverse clinical outcomes in a dose-dependent manner. Goreisan, a traditional Japanese herbal medicine, has a long history of use in Japan for regulating body fluid homeostasis and has been recognized as causing less adverse outcomes such as dehydration in contrast to loop diuretics in clinical practice. Therefore, we designed the GOREISAN-HF trial to evaluate the long-term effects of a new decongestion strategy adding Goreisan to usual care in patients with HF and volume overload. METHODS The GOREISAN-HF trial is an investigator-initiated, multicenter, pragmatic, randomized, comparative effectiveness trial in which we will enroll 2,192 patients hospitalized for HF at 68 hospitals in Japan. All study participants will be randomly assigned to either a decongestion strategy that adds Goreisan at a dose of 7.5 g daily on top of usual care or usual care alone. Investigators have the flexibility to change the existing diuretic regimen in both groups. The primary end point is the improvement rate of cardiac edema at 12-month follow-up, and the co-primary end point is a composite of all-cause death or hospitalization up to the end of the planned follow-up period. Secondary end points include longitudinal changes in patient-reported outcomes, loop diuretics dose, and renal function. CONCLUSIONS The GOREISAN-HF is the first large-scale randomized pragmatic trial to assess the efficacy and safety of a new congestion control strategy adding Goreisan to usual care in patients with HF and volume overload. REGISTRATION NUMBER NCT04691700.