Search

Optical image stabilization (OIS) systems maintain the three-dimensional focal position of a lens through mechanical actuation systems. This paper examines an optical lens for OIS that utilizes ultrasound vibration to alter the focal position, not only in the depth direction but also in the radial direction. The lens has a simple structure with no mechanical moving parts and consists of an ultrasound transducer divided into four pieces, a glass disk, and a transparent viscoelastic gel film that functions as a lens. The acoustic radiation force generated by the resonant flexural vibration of the glass disk can alter the surface profile of the gel film, allowing for a variable-focus function. The concave and convex lenses can be interchanged using two resonant vibration modes: the standing-wave mode, in which the vibration loop appears at the center, and the traveling-wave mode, in which the vibration node appears at the center. The positions of ultrasound vibrations on the lens can be controlled in a two-dimensional plane by adjusting the driving amplitudes of each channel, thereby achieving focus control in the radial direction. The focusing characteristics of the lens are evaluated through ray-tracing simulation. [ABSTRACT FROM AUTHOR]

Modulation of the refractive index in a medium by external stimuli enables fast and reversible control of light propagation. This technology for controlling light has led to new discoveries in a wide range of research fields from physics to life sciences and has played a major role in the development of photonics devices. In this article, we focus on ultrasound as an external stimulus and have devised a method to control the refractive index of a medium using ultrasound. Our research group has previously discovered that a giant refractive-index gradient (Δn on the order of 10−2) was induced when water was irradiated with high-frequency (100 MHz range), high-intensity (on the order of MPa) ultrasound. Here, we report ray-tracing simulations in a medium with a refractive-index gradient induced by ultrasonic radiation. A numerical model of the refractive-index gradient was developed based on the experimental data, and ray-tracing simulations were performed using the Euler–Lagrange equation. The ray-tracing simulation results were close numerically to the profiles of the laser beam observed in the experiment when the laser beam was incident on the refractive-index-gradient medium. [ABSTRACT FROM AUTHOR]

Proteolysis-Targeting Chimeras (PROTAC) are a bifunctional molecule that binds to a protein of interest (POI) and a ubiquitin ligase, thereby inducing the ubiquitination and degradation of POI. Many PROTACs currently utilize a limited number of ubiquitin ligases, such as von Hippel-Lindau (VHL) and Cereblon. Because these ubiquitin ligases are widely expressed in normal tissues, unexpected side effects can occur. Therefore, to expand the repertoire of ubiquitin ligases that can be utilized in PROTACs, we aimed to develop a versatile system to identify suitable novel ubiquitin ligases for PROTAC-mediated protein degradation using existing PROTACs. Chimeric ubiquitin ligases are constructed by fusing VHL with the ubiquitin ligase of interest that is stably expressed in cells. An existing PROTAC that binds to VHL was added to the cells, and the POI degradation activity was evaluated. In this study, we showed that epidermal growth factor receptor can be degraded by an existing PROTAC utilizing a chimeric ubiquitin ligase that fuses VHL and endoplasmic reticulum-localized ubiquitin ligase, HRD1. These results demonstrate that this novel approach can be used to identify suitable ubiquitin ligases for PROTAC-mediated degradation using existing PROTACs. Expanding the repertoire of ubiquitin ligases that can be utilized for PROTAC by using this versatile system is expected to enable the development of more effective and specific PROTACs for cancer and other diseases., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the preoperative risk factors for early intravesical recurrence after radical nephroureterectomy (RNU) in patients with upper urinary tract carcinoma (UTUC) according to the history of non-muscle invasive bladder cancer (NMIBC)., Methods: We retrospectively evaluated patients who underwent RNU for UTUC between 2012 and 2022 at 14 hospitals. Early recurrence was defined as intravesical pathologically confirmed recurrence within 1 year after RNU. Patients who received single-dose immediate intravesical instillation (IVI) as prevention for intravesical recurrence were excluded. Using preoperative factors, we examined the risk factors for early intravesical recurrences in patients with and without a history of NMIBC. Death from any cause within 1 year after RNU was regarded as a competitive risk., Results: We included 504 UTUC patients who were treated with RNU. Among these patients, 126 (25.0%) had a history of NMIBC, whereas 378 (75%) did not. According to multivariate analysis, the presence of macrohematuria, positive cytology in self-voided urine, and performing diagnostic ureteroscopy prior to RNU were risk factors in patients without a history of NMIBC. On the other hand, an NMIBC diagnosis within 1 year prior to RNU and an extravesical approach for bladder cuff management were risk factors in RNU-treated patients with a history of NMIBC., Conclusions: Early intravesical recurrence risk factors differ between UTUC patients with and without a history of NMIBC. Different stratification may be needed to predict intravesical recurrence risk in these two types of UTUC patients., (© 2025 The Japanese Urological Association.)

Introduction: The impact of atopic dermatitis (AD) on daily life and different levels of quality of life (QOL) according to AD severity has not been fully elucidated. This study aimed to assess QOL in relation to the AD severity in Japan., Methods: This observational study used anonymized data of health insurance association members and their families registered to a mobile health app. The QOL measures included the Dermatology Life Quality Index (DLQI), EuroQol five-dimensional five-level descriptive system (EQ-5D-5L), Work Productivity and Activity Impairment (WPAI), and sleep disturbance Numerical Rating Scale (NRS). The data were assessed according to AD severity: the Patient-Oriented Eczema Measure (POEM: 0-2, "clear/almost clear"; 3-7, "mild"; 8-16, "moderate"; 17-24, "severe"; 25-28, "very severe"); and itch NRS (0-10)., Results: Of 1507 adults with AD symptoms or undergoing treatments, 882 were identified with AD diagnosis records. Of those, 229 (26.0%), 242 (27.4%), 273 (31.0%), and 138 (15.6%) were included in the clear/almost clear, mild, moderate, and severe/very severe POEM groups, with mean ± standard deviation DLQI scores of 2.0 ± 2.7, 3.6 ± 3.3, 6.1 ± 4.4, and 10.4 ± 5.7, respectively. Higher DLQI scores were observed with increasing POEM severity and itch NRS (Spearman's rank correlation coefficient 0.629 and 0.615, respectively). EQ-5D-5L scores slightly lowered with increasing POEM severity, whereas WPAI percentage slightly increased. Sleep disturbance NRS increased with increasing AD severity in terms of POEM and itch NRS. Adults identified with AD diagnosis records (n = 882) yielded higher WPAI percentages than those without (n = 1204) in all four domains (Wilcoxon rank sum test, p < 0.001 for all)., Conclusion: This study, using real-world data in Japan, presented valuable data on the relationship between AD severity and various aspects of QOL. The data suggested greater QOL impairment with increasing AD severity; even at lower severity levels, QOL was impacted to some extent. The results highlight the need for careful consideration during clinical practice., Competing Interests: Declarations. Conflict of Interest: Hiroyuki Murota, has received consulting fees and/or speaker honoraria from Maruho Co., Ltd., Sanofi K.K., Pfizer Japan Inc., Torii Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., AbbVie GK, and Otsuka Pharmaceutical Co., Ltd. Takeshi Nakahara has received consulting fees and/or speaker honoraria from Mitsubishi Tanabe Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, Maruho, Sanofi, AbbVie, Eli Lilly Japan, Sun Pharma and Otsuka Pharmaceutical. Shinichi Noto has received speaker honoraria from Otsuka Pharmaceutical. Miyuki Matsukawa, Hiroe Takeda and Rikiya Toda are employees of Otsuka Pharmaceutical Co., Ltd. Ethical Approval: This study used secondary, anonymized data provided by DeSC. Therefore, no additional individual-level informed consent was obtained for conducting this study. The study protocol was approved by the Ethics Committee of Otsuka Pharmaceutical Co., Ltd. Research and Development Division, Research Ethics Committee (application and approval No. 221013). The questionnaire survey was conducted by DeSC in accordance with the Ethical Guidelines for Medical and Biological Research Involving Human Subjects in Japan and the Declaration of Helsinki., (© 2025. The Author(s).)

Introduction: We aimed to evaluate the efficacy and safety of enfortumab vedotin therapy for a cohort of older Japanese patients with metastatic urothelial carcinoma compared to younger patients., Materials and Methods: We retrospectively evaluated patients with metastatic urothelial carcinoma treated with enfortumab vedotin and recruited between April 2019 and February 2023. Older patients were defined as being ≥75 years old. Efficacy was evaluated by comparing overall survival, progression-free survival, and objective response rates between groups. Adverse events and relative dose intensity were also compared. Moreover, the prognostic factor for overall survival in the entire cohort was evaluated using multivariate analysis., Results: Of the 57 patients treated with enfortumab vedotin, 37 were younger and 20 were older, (median ages of 67.6 and 79.2, respectively). Median overall survival in older and younger patients was 407 and 365 days, respectively (P = 0.48). The objective response rate was 60.0 % and 54 % (P = 0.68) and median progression-free survival 228 and 223 days in older and younger patients, respectively (P = 0.76). Adverse events were equivalent between groups except for liver dysfunction, which frequently occurred in younger patients. The dose intensity for the older and younger patients did not differ (65.7 % vs. 63.5 %, P = 0.37, respectively). In multivariate analysis, neutrophil-to-lymphocyte ratio of 3 or more was the only risk factor for worse overall survival in the entire cohort (P = 0.04)., Discussion: Our data demonstrated that enfortumab vedotin therapy can benefit older patients with metastatic urothelial carcinoma equivalent to younger patients without compromising safety profiles., Competing Interests: Declaration of Competing Interest Naoya Masumori receives lecture fees from Astellas, AstraZeneca, Takeda, Kissei, and Jansen pharmaceutical, and research funding from Astellas, Takeda, Kissei, Ono pharmaceutical, Daiichi-Sankyo. Kohei Hashimoto receives honorarium from Bayer, Jansen pharmaceutical, Astellas, Astra Zeneca., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Despite of long-lasting tolvaptan treatment, individual renal outcomes are unclear in autosomal dominant polycystic kidney disease (ADPKD). This post-hoc analysis of the TEMPO 3:4 trial aimed to evaluate the predictability of estimated height-adjusted total kidney volume growth rate (eHTKV-α) on renal outcomes., Methods: In TEMPO 3:4, 1445 patients with ADPKD were randomised to tolvaptan or placebo for 3 years. The present analysis included patients with total kidney volume (TKV) data available at baseline and month 12 (tolvaptan, n = 812; placebo, n = 453); tolvaptan-assigned patients were grouped into quartiles based on percent change in eHTKV-α from baseline at 1 year. Clinical parameters were compared between quartiles, and regression analyses evaluated the predictive value of 1-year percent change in eHTKV-α and other factors on annual changes in TKV and estimated GFR (eGFR) over 3 years., Results: Trend tests identified significant differences between quartiles for several baseline parameters. Multivariate regression models confirmed that 1-year percent change in eHTKV-α was a significant predictor of annual changes in both TKV and eGFR over 3 years. Other significant predictors of annual changes in TKV and eGFR over 3 years were sex, age and body mass index, and first-year change in eGFR, race and baseline eGFR, respectively. Predicting factors using urine osmolality and plasma copeptin levels were not significant by backward stepwise selection analysis., Conclusions: 1-year percent change in eHTKV-α is useful biomarker to identify treatment good responders and may be utilized for early estimate of trial outcomes of new drugs in ADPKD., Competing Interests: Declarations. Conflict of interest: EH has no conflict of interest to declare. MM is an employee of Otsuka Pharmaceutical Co., Ltd., Japan. HJ is an employee of Otsuka Pharmaceutical Development & Commercialization, USA., (© 2024. The Author(s).)

We surveyed the status of the secondary finding (SF) disclosure in comprehensive genome profiling (CGP) in 2020. The situation has changed: increase in the number of hospitals that provide CGP, an update to the Comprehensive Tumor Genomic Profiling: Materials for Review of Secondary Findings (CTGPMRSF), and the addition of a liquid biopsy test, FoundationOne ® Liquid CDx (F1L). Moreover, the actual situation was unclear because the 2020 survey did not include all designated and cooperative hospitals. Herein, we conducted a questionnaire survey of all designated-core, designated, and cooperative hospitals to identify the current status and challenges concerning SF in the CGP in 2022. A total of 82.1% of the hospitals responded and 77.7% of the response was from cooperative hospitals. Approximately 80% of the hospitals used CTGPMRSF. SF disclosure, confirmatory test implementation, and SF confirmation rates were 12.4%, 31.6%, and 46.6% for FoundationOne ® CDx (F1CDx), respectively, and 6.8%, 31.8%, and 70.7% for F1L, respectively. The implementation rate of the confirmatory test was substantially higher in hospitals with genetic experts and in hospitals that could conduct confirmatory tests on the same day. Our survey provides insight into how SF is handled in Japan. The percentage of cases leading to confirmatory tests has gradually increased, although challenges such as insurance coverage limitations and varied understanding of SF among patients and healthcare providers persist. With the increasing use of whole-genome analysis, our findings will provide valuable insights into establishing an effective SF disclosure system., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Purpose: To conduct a longitudinal evaluation of sites grafted with autogenous bone prior to implant placement using a dental cast with a 3D modeling system., Materials and Methods: A total of nine patients underwent implant treatment with bone grafting for anterior missing teeth. Informed consent was obtained from each patient. Casts were made and evaluated at three time periods, including before bone grafting (Pre BG), 4 or 5 months after grafting (Post BG), and 4 or 5 months after implant placement (Post IP). 3D data of these casts were acquired using a 3D digital scanner and then superimposed with reference to the remaining teeth. The volume of the anterior area of the cast was evaluated Pre BG and Post BG., Results: Accuracy of superimposition on the remaining teeth was between 20 and 50 µm. Horizontal differences Post BG and Post IP were 0.1 to 1.6 mm. The volume Post IP decreased by 14% to 38% compared to the volume Post BG., Conclusions: This 3D modeling technique allowed 3D evaluation before and after bone grafting. Results suggested that the volume of the maxilla was sequentially decreased after bone grafting.

We report here a rare case of a concurrent occurrence of abscesses caused by  Staphylococcus aureus  in the prostate, seminal vesicles, and epididymis. A 71-year-old male presented to our hospital with urinary retention, and an indwelling urethral catheter was inserted. He remained afebrile until a revisit one month later when he developed a fever and left scrotal swelling. Imaging studies revealed multiple abscesses in the left lobe of the prostate, bilateral seminal vesicles, and the left epididymis. Ceftriaxone was initiated upon admission and was administered for five days before switching to cefazolin for an additional 11 days. From the sixth day of admission, levofloxacin was added to ensure adequate prostatic tissue penetration until the 18th day. Owing to his poor response to antimicrobial chemotherapy, percutaneous prostatic needle aspiration, percutaneous cystostomy, transurethral deroofing of the abscess, and left orchiectomy were performed on the eighth day. Methicillin-susceptible  S. aureus  was isolated from the urine and abscess fluid. The patient had no recurrence at one year postoperatively. A prostate abscess may not manifest as fever or elevated prostate-specific antigen levels, even when  S. aureus is the causative agent, and can lead to delayed diagnosis and subsequent involvement of the seminal vesicles and epididymis., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Ethics Committee of Takikawa Municipal Hospital issued approval with approval no. 23-05. The protocol for this research project conforms to the provisions of the Declaration of Helsinki. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nakamura et al.)

Aims: To help establish optimized treatment strategies for congestion in patients with acute heart failure, this study aimed to provide a detailed summary of real-world diuretic use in hospitalized patients with heart failure requiring urgent therapy in Japan., Methods and Results: This observational study used a Japanese medical records database to extract data of patients admitted to hospital with a heart failure diagnosis and an intravenous diuretic prescription from the day before admission to 2 days after. Time from hospital visit to first dose, second dose, and maximum dose of intravenous diuretics were determined. Patients were grouped according to whether they received diuretic modification, defined as an intravenous diuretic dose increase or concomitant use of other diuretics., Results: Overall, 1577 patients were included in the study (without diuretic modification, n = 1140 [72.3%]; with diuretic modification, n = 437 [27.7%]). The study population was 49.5% female (n = 780) and the mean age ± standard deviation was 80.1 ± 12.7 years. Intravenous diuretic treatment was received within 1 h of their hospital visit in 43.5% of patients (686/1577) and ≤2 h in 16.4% of patients (258/1577). Among 437 patients with an inadequate response following their first dose, 42.1% received an intravenous dose titration, 56.5% received combination diuretics, and 1.4% received both. Over half of the patients (59.0% [258/437]) with diuretic modification received it after the first 24 h of the hospital visit. The median time from hospital visit to first dose titration was similar to time to first combination diuretic use (18.6 h and 17.0 h, respectively). The mean ± standard deviation duration of intravenous diuretic use was significantly longer for patients with versus without diuretic modification (6.3 ± 5.2 vs. 3.7 ± 3.2 days), and a significantly greater proportion of patients (44.6% [195/437] vs. 35.0% [399/1140]) received repeated intravenous diuretic administration. Other characteristics/outcomes of intravenous diuretic use were similar with versus without diuretic modification, including in-hospital death (15.6% [68/437] vs. 13.9% [159/1140]) and mean ± standard deviation length of hospitalization (21.9 ± 14.7 days vs. 22.1 ± 21.2 days)., Conclusions: In Japan, real-world patterns of intravenous diuretic administration for patients with heart failure remains far from the time-sensitive approach recommended in Japanese, European, and United States guidelines., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: Difamilast has proven to be an effective treatment for the treatment of atopic dermatitis (AD) in Japan, but its cost-effectiveness remains unknown. Therefore, the objective of the current study was to determine the cost-effectiveness of difamilast 1% compared with delgocitinib 0.5% in Japanese adult patients with moderate-to-severe AD and compared with placebo in Japanese adult patients with all-severity AD from a Japanese public health-care perspective., Methods: The analysis was conducted using a cost-effectiveness model from the Japanese public health-care perspective. This model had four health states ("clear," "mild," "moderate," and "severe") defined according to the Eczema Area and Severity Index score. The time horizon of the analysis was 1 year. Because the analysis period was short, no discount rate was applied. The proportions of patients previously estimated by the anchored matching-adjusted indirect comparison were implemented in the model. The model was further populated with data from the literature. The main model outcomes were quality-adjusted life-years (QALY), costs, and outcomes, including the incremental cost-effectiveness ratio. All prices were stated in JPY at the price level from 2018 April to 2019 March. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were performed to assess the robustness of the results., Results: In the base case, the cost-effectiveness of difamilast 1% compared with delgocitinib 0.5% and placebo was JPY 827,054/QALY and JPY 1,518,657/QALY, respectively. The PSA showed that the cost-effectiveness of difamilast 1% compared with delgocitinib 0.5% and placebo had a 66.6% and 99.6% probability of being below the JPY 5 million/QALY threshold, respectively., Conclusion: The results suggest that difamilast 1% is a more cost-effective treatment option compared with delgocitinib 0.5% in Japanese adult patients with moderate-to-severe AD and compared with placebo in adult patients with all-severity AD from a Japanese public health-care perspective., Competing Interests: Declarations Conflict of Interest Takeshi Nakahara has received consulting fees and/or speaker honoraria from Mitsubishi Tanabe Pharma Corporation, Taiho Pharmaceutical Co., Ltd., Torii Pharmaceutical Co., Ltd., Maruho Co., Ltd., Sanofi K.K, AbbVie GK, Eli Lilly Japan K.K., Sun Pharma Japan Ltd., and Otsuka Pharmaceutical Co., Ltd. Shinichi Noto received speaker honoraria from Otsuka Pharmaceutical Co., Ltd. Miyuki Matsukawa, Hiroe Takeda, Yilong Zhang, and Tomohiro Kondo are employees of Otsuka Pharmaceutical Co., Ltd. The funders provided only the funds necessary for this study, and there were no factors that significantly influenced the results. The study was started after obtaining approval through the Otsuka Pharmaceutical theme evaluation. Ethical Approval This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors., (© 2024. The Author(s).)

Huntington's disease (HD) is a neurodegenerative disease with autosomal dominant inheritance, and no radical cure for HD has been established. Qualitative studies are necessary to investigate the psychological state of individuals who underwent predictive testing for HD, because the psychosocial impact on noncarriers remains unclarified in Japan. Herein, we elucidated the psychosocial impact on the noncarriers for HD and the role of genetic counseling for predictive testing and follow-up after testing by examining their experiences with predictive testing. We conducted semi-structured interviews with eight individuals participating in this study. Interview data were transcribed verbatim and evaluated according to thematic analysis. As a result, 4 themes were generated from 21 categories of 46 codes: (1) Diversity of perceptions concerning the test results, (2) Views on life as a noncarrier, (3) Changes in feelings toward and relationships with family members, and (4) Sharing information within the family. After receiving the negative results, the noncarriers felt not only relief but also surprise, doubt, relief from tension, and regret. It was shown that noncarriers felt survivor's guilt toward many unspecified individuals, which was not only a sense of guilt but also a sense of mission or responsibility. Additionally, they conducted altruistic behavior as members of their family and society, that may be related to the Japanese collectivism. Some participants were concerned about sharing information with their siblings. Noncarriers for HD can experience complex psychological states, and Japanese people who prefer high-context communication may find it difficult to express their feelings and thoughts. It is important to understand their true feelings before and after the predictive genetic testing, reconsider the impact of being a noncarrier and whether it is a burden for them from both subjective and objective perspectives, and conduct long-term follow-up as needed., (© 2024 National Society of Genetic Counselors.)

Background: Atopic dermatitis (AD) is a chronic condition with an increasing incidence in Japan. Difamilast and delgocitinib are both new topical drugs for AD proven to be efficacious and safe in phases 2 and 3 clinical trials in Japan. However, there are no head-to-head trials comparing their efficacy and safety. The aim of this study was to determine the proportion of patients by severity and compare the clinical efficacy and safety of difamilast with delgocitinib among patients with moderate-to-severe AD using a matching-adjusted indirect comparison (MAIC)., Methods: Phase 3 clinical trials of difamilast and delgocitinib for treating AD were included. The trials had similar designs but differed in baseline population characteristics. Anchored MAIC was used to align the baseline characteristics and calculate clinical outcomes. The primary outcome was to determine severity stages of the proportion of patients with AD through Eczema Area and Severity Index (EASI), while the secondary outcome included comparing other clinical efficacy and safety of difamilast with delgocitinib., Results: A total of 340 patients were selected (170 each received difamilast and placebo) from the difamilast trial, with 158 (106 received delgocitinib; 52 received placebo) from the delgocitinib trial for the analysis. After matching patients from the difamilast trial with those from the delgocitinib trial, the effective sample sizes (ESS) reduced to 32.7-43.3% of the original difamilast (treatment/placebo) patients. At week 4, the ESS in the difamilast group demonstrated no statistically significant differences in the distribution of AD severity stages, as per EASI scores, compared with the delgocitinib group. In addition, no significant differences were found in modified EASI (mEASI) scores, mEASI 50 and 75 scores, and safety outcomes between the two treatments., Conclusions: The anchored MAIC analysis indicates that difamilast treatment, like delgocitinib, is a useful option for the treatment of patients with moderate-to-severe AD in Japan., (© 2024. The Author(s).)

Delayed cardiac tamponade following blunt chest trauma is a rare incident, and we provide a report including a literature review for further discussion. The patient is a 56-year-old male. He fell off a motorcycle and sustained contusions to the left side of his chest. He presented to our emergency department. His consciousness was clear and vital signs were normal. Computed tomography (CT) scan revealed multiple left rib fractures, left hemothorax, and left pulmonary contusion, but no pericardial effusion was detected. He returned home, and stayed at rest for a few days. He walked for 15 minutes on the third day after the injury, and he felt unwell and visited our emergency department again in a state of shock. Echocardiography and CT scan revealed significant amount of pericardial effusion, and emergency surgery was indicated. At surgery, bleeding site near the left ventricule (LV) apex was identified and hemostasis was achieved through median sternotomy. We should be careful of delayed cardiac tamponade after blunt chest trauma.

Objective: This study aimed to describe the migraine burden and healthcare utilization in the context of headache frequency using nationwide claims data linked to online survey data previously collected in Japan., Background: It has been shown that increase in headache frequency can impose greater impact on individuals' daily and social functioning, but migraine burden in those with low-frequency headaches remains largely unknown in Japan., Methods: This post-hoc , observational study reported on 674 respondents who were working individuals and their family members aged 19-74 years, responded to an online questionnaire (response rate: 14.1% [21,704 responded/153,545 kencom Ⓡ registrants]), and were previously classified as having migraine. Disease burden in terms of Migraine-Specific Quality of Life (MSQ) and Work Productivity and Activity Impairment (WPAI) was compared across 0-3, 4-7, 8-14, and ≥ 15 monthly headache days (MHD)., Results: Among 674 respondents, 419 (62.2%), 148 (22.0%), 61 (9.1%), and 46 (6.8%) had 0-3, 4-7, 8-14, and ≥ 15 MHD, respectively. Of those, 55 (13.1%), 31 (20.9%), 19 (31.1%), and 20 (43.5%) respondents consulted physicians for headaches. Moderate-to-severe impairments in daily activities were reported by 298 (71.1%), 110 (74.3%), 46 (75.4%), and 38 (82.6%) respondents. The proportion of the respondents with WPAI >0% generally increased with increasing headache frequency (presenteeism: 41.7 and 67.5% in respondents with 0-3 and ≥ 15 MHD, respectively; overall work impairment: 44.8 and 72.5%, respectively; and activity impairment: 44.9 and 73.9%, respectively), except for absenteeism (12.4 and 22.5%, respectively). The mean MSQ score declined with increasing MHD (Role function-restrictive: 75.1 and 59.5 in those with 0-3 and ≥ 15 MHD, respectively; Role function-preventive: 85.8 and 75.0, respectively; and Emotional function: 81.9 and 63.6, respectively)., Conclusion: Based on the Japanese nationwide claims data, quality of life and work productivity decreased with increasing numbers of headache days. Substantial disease burden paired with low levels of healthcare utilization highlights the need for medical or non-medical intervention., Competing Interests: RI has served as a consultant for Amgen K.K., Eli Lilly Japan K.K., DAIICHI SANKYO COMPANY, LIMITED, and Otsuka Pharmaceutical Co., Ltd. He has received lecture fees from Amgen K.K., Eli Lilly Japan K.K., DAIICHI SANKYO COMPANY, LIMITED, and Otsuka Pharmaceutical Co., Ltd. FS has received consulting fees from Otsuka, Amgen, Eli Lilly, and AbbVie. HS, MN, and MM are employees of Otsuka Pharmaceutical Co., Ltd., and NK is a previous employee of Otsuka Pharmaceutical Co., Ltd. The authors declare that this study received funding from Otsuka Pharmaceutical Co., Ltd. The funder was involved with the study design, collection, analysis, interpretation of data, the writing of this article, and the decision to submit it for publication., (Copyright © 2024 Ishii, Sakai, Sano, Nakai, Koga and Matsukawa.)

Introduction: Antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using the national surveillance data, comprising 793 bacterial strains from eight clinically relevant species., Materials and Methods: Data were collected for the fourth national surveillance project from July 2020 to December 2021 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was supervised with the cooperation of 43 medical institutions throughout Japan., Results: Fluoroquinolone required a minimum inhibitory concentration (MIC) of 2-64 mg/L to inhibit the 330 tested Escherichia coli strains. The proportion of levofloxacin-resistant E. coli strains increased from 28.6% in 2008 to 29.6% in 2011, 38.5% in 2015, and 44.5% in 2021. The proportion of levofloxacin-resistant strains of Pseudomonas aeruginosa also increased from previous survey results, showing a continuing downward trend. Conversely, the proportion of levofloxacin-resistant strains of Enterococcus faecalis decreased relative to previous reports. Neither multidrug-resistant P. aeruginosa nor carbapenem-resistant Enterobacteriaceae were detected. For methicillin-resistant Staphylococcus aureus (MRSA), the proportion of vancomycin-susceptible strains (MIC of 2 μg/mL) decreased from 14.7% to 7.7%., Discussion: Bacterial strains that produced extended-spectrum β-lactamase included E. coli (82/330 strains, 24.8%), Klebsiella pneumoniae (11/68 strains, 16.2%), and Proteus mirabilis (4/26 strains, 15.4%). As compared to previous surveillance reports, these strains showed an increase in proportion over the years., Competing Interests: Declaration of competing interest Satoshi Takahashi received speaker honoraria from Fujirebio Inc. and research funding from Shino-Test Corporation, Roche Diagnostic K. K., Fujirebio Inc., and Abbott Japan Co., Ltd. Koichiro Wada received speaker honoraria from Janssen Pharmaceutical K.K., and MSD K.K. Shingo Yamamoto received speaker honoraria from MSD K.K., Fuso Pharmaceutical Industries, Ltd., Daiichi Sankyo Co., Ltd. and scholarship donations from Takeda Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd. and research funding from Takeda Pharmaceutical Co., Ltd. Tetsuya Matsumoto received speaker honoraria from MSD K.K., Pfizer Japan Inc., and Kyorin Pharmaceutical Co., Ltd., and research funding from Kewpie Corporation., Biofermin Pharmaceutical Co., Ltd. Kazumasa Matsumoto received research funding from Sysmex Corporation. Tohru Nakagawa received speaker honoraria from Astellas Pharma Inc., AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., and Janssen Pharmaceutical K.K., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: There is a concern that the coronavirus disease 2019 (COVID-19) pandemic has led to underutilization of non-invasive positive pressure ventilation (NPPV) in patients with acute heart failure (HF). We investigated the alterations in clinical management of acute HF during the COVID-19 pandemic., Methods and Results: This study was an observational study of patients treated in emergency care with acute HF, using a Japanese Administrative database for a period before and during the COVID-19 pandemic. Of the 9081 overall eligible patients, the ratio of patients receiving NPPV and tracheal intubation during to before the COVID-19 pandemic were 0.88 [95 % confidence interval (CI): 0.80, 0.96] and 1.38 (95 % CI: 1.11, 1.71), respectively. Propensity score matching in patients treated in COVID-19 receiving facilities and emergency declaration response areas showed that ratio of NPPV and tracheal intubation during to before the COVID-19 pandemic were 0.88 (95 % CI: 0.76, 1.03), and 1.65 (95 % CI: 1.19, 2.28), respectively., Conclusions: The implementation rate of NPPV decreased significantly in eligible patients, with a decreasing trend observed in patient populations in COVID-19 receiving facilities and emergency declaration response areas. Tracheal intubation increased in all populations., Competing Interests: Declaration of competing interest Tatsuhiro Shibata has received honoraria from AstraZeneca KK, Daiichi Sankyo Co., Ltd., Novartis Pharmaceuticals KK, and Otsuka Pharmaceuticals Co., Ltd. Shingo Matsumoto received personal lecture fees from Abbott, Bayer Pharma, Boehringer Ingelheim, Medtronic, Novartis, Ono Pharma, OrbusNeich, and Otsuka Pharma. Tomoki Muramoto and Miyuki Matsukawa are employees of Otsuka Pharmaceutical Co., Ltd., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To explore pre-treatment risk factors for overall survival (OS) in advanced urothelial carcinoma (UC) patients treated with first-line (1L) chemotherapy in sequential therapy (ST) era. Additionally, to evaluate the proportion of patients who were not able to undergo subsequent immune checkpoint inhibitor (ICI) therapy according to the subgroups stratified by the risk factors., Methods: A multicenter retrospective study was conducted. Metastatic or locally advanced UC patients treated between 2017 and 2022 were included. The Kaplan-Meier method with the log-rank test and multivariate Cox regression models were used to address OS., Results: Three hundred and fourteen patients treated with 1L chemotherapy were included in the study and 57 (18.2%) patients were not able to proceed to subsequent ICI therapy. Pre-chemotherapy risk factors for OS in 314 patients were ECOG-PS 1 or more, having no primary site resection, C-reactive protein (CRP) level of 3 mg/dL or more, and non-cisplatin-based regimen. Patients having 3 or 4 risk factors had higher risk for not being able to receive ST (Mann-Whitney U test, P < 0.001). As risk factors for OS in 230 patients who were able to receive ST, having no primary site resection, a neutrophil to lymphocyte ratio of 3 or more, and the presence of liver metastasis were identified., Conclusion: We reported the risk factors for OS in advanced UC patients treated with 1L chemotherapy in ST era. Patients with high risk for OS may not be able to proceed to subsequent ICI therapy even in the ST era., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Radiolabeled antibodies are promising tools for cancer diagnosis using nuclear medicine. A DOTA-chelating system is useful for preparing immuno-positron emission tomography and immuno-single-photon emission computed tomography probes with various radiometals. Radiolabeled antibodies are generally metabolized in the reticuloendothelial system, producing radiometabolites after proteolysis in hepatic lysosomes. Because of the bulkiness and extremely high hydrophilicity of DOTA, radiometabolites containing a radiometal-DOTA complex typically exhibit high and persistent localization in hepatic lysosomes. Radioactivity in the liver impairs the accurate diagnosis of cancer surrounding the liver and liver metastasis, and a high tumor/liver ratio is desirable. In this study, we reduced the hepatic radioactivity of radiometal-labeled antibodies containing a DOTA-chelating system. A cleavable linkage was inserted to liberate the radiometabolite, which exhibited a short residence time in hepatocytes., Methods: Using indium-111 ( 111 In)-labeled antibodies, we prepared 111 In-labeled galactosyl-neoglycoalbumins (NGAs) because they are useful for evaluating the residence time of radiometabolites in the liver. An 111 In-labeled NGA with a cleavable linkage ([ 111 In]In-DO3AiBu-Bn-FGK-NGA) was administered to normal mice, and biodistribution studies and metabolic analyses of urinary and fecal samples were performed with comparison to an 111 In-labeled NGA prepared by a conventional method ([ 111 In]In-DOTA-Bn-SCN-NGA). Then, 111 In-labeled antibodies ([ 111 In]In-DO3AiBu-Bn-FGK-IgG and [ 111 In]In-DOTA-Bn-SCN-IgG) were prepared using a procedure similar to that for 111 In-labeled NGAs. In vitro plasma stability and biodistribution were investigated for both 111 In-labeled antibodies in U87MG tumor-bearing mice., Results: Through the liberation of radiometabolites including [ 111 In]In-DO3AiBu-Bn-F, [ 111 In]In-DO3AiBu-Bn-FGK-NGA was cleared more rapidly from the liver than [ 111 In]In-DOTA-Bn-SCN-NGA (4.07 ± 1.54%ID VS 71.68 ± 3.03%ID at 6 h postinjection). [ 111 In]In-DO3AiBu-Bn-FGK-IgG exhibited lower tumor accumulation (8.83 ± 1.48%ID/g) but a significantly higher tumor/liver ratio (2.21 ± 0.53) than [ 111 In]In-DOTA-Bn-SCN-IgG (11.65 ± 2.17%ID/g in the tumor and a tumor/liver ratio of 0.85 ± 0.18) at 72 h after injection., Conclusion: A molecular design that reduces the high and persistent hepatic radioactivity of radiolabeled antibodies by liberating radiometabolites with a short hepatic residence time in lysosomes would be applicable for radiometal-labeled antibodies using a DOTA-chelating system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This retrospective observational study investigated the incidence of worsening renal function (WRF) in patients hospitalized for heart failure (HF) and treated with intravenous diuretics in Japan., Methods and results: Associations between WRF at any point and HF treatments, and the effects of WRF on outcomes were evaluated (Diagnosis Procedure Combination database). Of 1,788 patients analyzed (mean [±SD] age 80.5±10.2 years; 54.4% male), 641 (35.9%) had WRF during a course of hospitalization for worsening HF: 208 (32.4%) presented with WRF before admission (BA-WRF; estimated glomerular filtration rate decreased by ≥25% from baseline at least once between 30 days prior to admission and admission); 44 (6.9%) had WRF that persisted before and after admission (P-WRF); and 389 (60.7%) had WRF develop after admission (AA-WRF). Delayed initial diuretic administration, higher maximum doses of intravenous diuretics during hospitalization, and diuretic readministration during hospitalization were associated with a significantly higher incidence of AA-WRF. Patients with WRF at any time point were at higher risk of death during hospitalization compared with patients without WRF, with adjusted hazard ratios of 3.56 (95% confidence interval [CI] 2.23-5.69) for BA-WRF, 3.23 (95% CI 2.21-4.71) for AA-WRF, and 13.16 (95% CI 8.19-21.15) for P-WRF (all P<0.0001)., Conclusions: Forty percent of WRF occurred before admission for acute HF; there was no difference in mortality between patients with BA-WRF and AA-WRF.

Compound lens systems with mechanical actuators are used to focus objects at near to far distances. The focal length of ultrasound varifocal liquid crystal (LC) lenses can be controlled by modulating the refractive index spatial distribution of the medium through the acoustic radiation force, resulting in thin and fast-response varifocal lenses. The frequency characteristics of such a lens are evaluated in this paper, and several axisymmetric resonant vibration modes over 20 kHz are observed. The effective lens aperture decreased with the wavelength of the resonant flexural vibration generated on the lens, meaning that this parameter can be controlled with the driving frequency.

We aimed to survey the status of tolvaptan administration in routine clinical practice since the approval of a novel indication for treating syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in Japan. Data from a population of 3,152 patients aged ≥18 years and diagnosed with SIADH between July 1, 2020 and June 30, 2021 were extracted from a Japanese database. Tolvaptan was administered to 586 patients while 2,566 patients were followed up without tolvaptan. In the tolvaptan-treated group, the standard initial doses were 3.75 mg and 7.5 mg in 290 (49.5%) and 250 (42.7%) patients, respectively. The dose was increased in 112 (38.6%) and 71 (28.4%) and decreased in 8 (2.8%) and 46 (18.4%) of patients with 3.75 and 7.5 mg initial doses, respectively. Of the total 586 SIADH patients treated with tolvaptan, serum sodium concentrations were analyzed in 60 patients. In both treatment groups of 3.75 and 7.5 mg initial doses, the serum sodium concentration was elevated from the second day of treatment and reached 135 mEq/L on the fourth day, which was maintained for 2 weeks. Rapid correction of hyponatremia (>10 mEq/L increase in serum sodium concentration over 1 day or >18 mEq/L increase over 2 days) occurred in 26.7% patients with a 7.5 mg initial dose (4 of 15 patients) but not in the patients with a 3.75 mg initial dose (n = 16), suggesting that an initial dose of 3.75 mg of tolvaptan may be a better choice for the safe and proper correction of hyponatremia.

Purpose: To evaluate the significance of local radiation therapy (LRT) for prevention of local symptoms (LSs) caused by muscle-invasive bladder cancer (MIBC)., Methods: We retrospectively reviewed the clinical records of 133 patients from 13 hospitals. MIBC patients with or without metastases who were treated with LRT alone from January 2015 through December 2020 were enrolled. Exclusion criteria were urinary diversion (UD) prior to LRT, non-MIBC, or lack of clinical information. LSs were defined as hematuria requiring invasive treatment or transfusion, UD after LRT, bladder tamponade, and opioid use for bladder pain., Results: One hundred fourteen patients were finally enrolled in the study. During the median follow-up period of 13.5 months, 30 patients (26.3%) had LSs. Risk factors of LSs in multivariate analysis were a prior history of non-MIBC (NMIBC) (hazard ratio [HR] 2.99; 95% confidence interval [CI], 1.36 to 6.56; P < 0.01), radiation dose of less than 50 Gray (Gy) (HR 3.99; 95% CI, 1.80 to 8.82; P < 0.01), and tumor stage 3 or more (HR 2.43; 95% CI, 1.14 to 5.21; P = 0.02). Risk factors of overall survival (OS) in multivariate analysis were being female (HR 3.32; 95% CI, 1.68 to 6.58; P < 0.01), an age-adjusted Charlson Comorbidity index of 6 or more (HR 2.19; 95% CI, 1.18 to 4.10; P = 0.01), distant metastases (HR 3.20; 95% CI, 1.39 to 6.58; P < 0.01), and tumor size of 40 mm or more (HR 2.38; 95% CI, 1.34 to 4.52; P < 0.01). Toxicity (all grades) occurred in 40.4% of the patients, 4.8% with grade 3 or more and 95.2% with lower grades., Conclusions: We determined the risk factors for LSs in MIBC patients treated with LRT alone. An escalated-dose of 50 Gy or more may contribute to prevention of LSs caused by MIBC. Thus, dose-escalated LRT for MIBC patients who can expect favorable survival may be a good option to avoid future annoying LSs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Low-intensity pulsed ultrasound treatment is known to shorten the healing period of bone fractures by 30%-40%, but the initial mechanism of the healing process remains unknown. One possible mechanism is related to the piezoelectricity of bone. However, the complex geometry of bones results in inherent challenges to evaluating electric fields induced therein. Therefore, in this study, we investigate the piezoelectric responses of bones by using simulations to study the wave propagation and induced potentials in bone, according to the piezoelectric finite-difference time-domain (PE-FDTD) method. First, we verify the suitability of the PE-FDTD method by comparing the simulated electric field results with the experimental data obtained by an ultrasound receiver using bone as the piezoelectric element. Next, ultrasound irradiation into a real bone model (the radius of a 66-year-old woman) is simulated at different incident angles. At normal incidence and off-axis incidence (45°), the maximum electric field strength was 4.3 and 5.6 mV/cm, respectively. We also present evidence of significant shear wave contribution to the induced potential. The results of this study confirm the existence of ultrasonically induced potentials in heterogenous bones with complex shapes, equal in magnitude to potentials generated in electrically stimulated bone healing., (© 2023 Acoustical Society of America.)

Introduction: Collision tumors are a rare phenomenon defined as two or more histologically distinct tumors that are in contact with each other., Case Presentation: The patient was a man with a history of end-stage diabetic nephropathy under hemodialysis treatment for 15 years. A plain computed tomography scan showed a 4.3 cm mass with obscured margins in the right perirenal fat of the lower pole kidney. On T 2 -weighted magnetic resonance imaging, the lesion showed heterogeneous signal intensity with a partially cystic component. A radical nephrectomy was performed. Histopathological and immunohistochemical examination revealed collision tumors constituted of a spindle cell lipoma covering the kidney surface underneath the perirenal fat and diffusely distributed acquired cystic disease-associated renal cell carcinoma in the renal parenchyma., Conclusion: We report the first case of collision tumors comprising spindle cell lipoma and acquired cystic disease-associated renal cell carcinoma., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

Background: The impact of tolvaptan on the long-term outcomes of patients with heart failure (HF) remains inconclusive. We evaluated patients requiring long-term congestion management for the time to rehospitalization for HF (HF rehospitalization), the time to in-hospital death and explored the factors that may influence the outcomes., Methods: Using data (April 2008 to September 2019) from a medical claims database, patients with HF prescribed tolvaptan (tolvaptan cohort) and those prescribed loop diuretics before tolvaptan was introduced to the hospital (furosemide cohort) were compared. Patients with HF who experienced ≥2 HF hospitalizations and ≥1 tolvaptan or loop diuretic prescription during and after HF hospitalization were included. Data of patients with serum creatinine and estimated glomerular filtration rate were analyzed for time to HF rehospitalization and in-hospital death within 1 year after the second discharge and factors that may influence the outcomes., Results: Among the 1931 and 631 tolvaptan and furosemide cohort patients, respectively, time to HF rehospitalization was not significantly different (p = 0.0921); time to in-hospital death was significantly longer in the tolvaptan cohort than in the furosemide cohort (p = 0.0005). Age, serum sodium, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were identified as factors for both outcomes (p < 0.05)., Conclusions: Tolvaptan did not significantly affect time to HF rehospitalization. However, further worsening of the condition leading to death may be delayed, and time to in-hospital death may be prolonged in patients treated with tolvaptan, indicating its usefulness for long-term congestion management., Competing Interests: Declaration of competing interest Koichiro Kinugawa received consultancy fees, lecture fees, manuscript fees for writing of a leaflet and scholarship funds from Otsuka Pharmaceutical Co., Ltd. Miyuki Matsukawa, Yumiko Nakamura, Miki Aihara, and Hiromi Sano are employees of Otsuka Pharmaceutical Co., Ltd., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Surface plasmon resonance (SPR) type ultrasonic sensors enable local measurements and have a flat frequency response in a wide frequency range. They are expected to be used in photoacoustic microscopy (PAM) and other applications that require broadband ultrasonic detection. In this study, we focus on the precise measurement of ultrasound pressure waveforms via a Kretschmann-type SPR sensor. The noise equivalent pressure was estimated to be 52 Pa [Formula: see text], and the maximum amplitude of the wave measured via the SPR sensor linearly responded to the pressure until 427 kPa [Formula: see text]. Furthermore, the observed waveform for each applied pressure agreed well with the waveforms measured via the calibrated ultrasonic transducer (UT) in the MHz range. Moreover, we focused on the effect of the sensing diameter on the frequency response of the SPR sensor. The results show that the beam diameter reduction improved the frequency response at high frequencies. Evidently, we found that the sensing diameter of the SPR sensor must be carefully selected in consideration of the measurement frequency.

Numerous studies report that perioperative oral care decreases the frequency of postoperative pneumonia or infection. However, no studies have analyzed the specific impact of oral infection sources on the postoperative course, and the criteria for preoperative dental care differ among institutions. This study aimed to analyze the factors and dental conditions present in patients with postoperative pneumonia and infection. Our results suggest that general factors related to postoperative pneumonia, including thoracic surgery, sex (male > female), the presence or absence of perioperative oral management, smoking history, and operation time, were identified, but there were no dental-related risk factors associated with it. However, the only general factor related to postoperative infectious complications was operation time, and the only dental-related risk factor was periodontal pocket (4 mm or higher). These results suggest that oral management immediately before surgery is sufficient to prevent postoperative pneumonia, but that moderate periodontal disease must be eliminated to prevent postoperative infectious complication, which requires periodontal treatment not only immediately before surgery, but also on a daily basis.

Rapid reperfusion therapy can reduce disability and death in patients with large vessel occlusion strokes (LVOS). It is crucial for emergency medical services to identify LVOS and transport patients directly to a comprehensive stroke center. Our ultimate goal is to develop a non-invasive, accurate, portable, inexpensive, and legally employable in vivo screening system for cerebral artery occlusion. As a first step towards this goal, we propose a method for detecting carotid artery occlusion using pulse wave measurements at the left and right carotid arteries, feature extraction from the pulse waves, and occlusion inference using these features. To meet all of these requirements, we use a piezoelectric sensor. We hypothesize that the difference in the left and right pulse waves caused by reflection is informative, as LVOS is typically caused by unilateral artery occlusion. Therefore, we extracted three features that only represented the physical effects of occlusion based on the difference. For inference, we considered that the logistic regression, a machine learning technique with no complex feature conversion, is a reasonable method for clarifying the contribution of each feature. We tested our hypothesis and conducted an experiment to evaluate the effectiveness and performance of the proposed method. The method achieved a diagnostic accuracy of 0.65, which is higher than the chance level of 0.43. The results indicate that the proposed method has potential for identifying carotid artery occlusions., (© 2023. The Author(s).)

Background: Intravenous (IV) diuretics are key in the treatment of acute heart failure, but the time of administration can affect outcomes. Using a medical database, we assessed the real-world usage and clinical impact of IV diuretics after admission. Methods and Results: This observational study included hospitalized patients with heart failure who received IV diuretics. Relationships between IV diuretic use and clinical outcomes (duration of hospitalization, in-hospital mortality, readmission) were evaluated using analysis of variance or logistic regression. Overall, 9,653 patients (51.1% male) were assessed (mean age 80.9 years). Most (89.1%) patients had IV loop diuretic treatment initiated on Day 1 of hospitalization and 68.0% achieved the maximum dose on that day. The median duration of hospitalization was 17.0 days. In-hospital mortality was 9.2%; 13.7% of patients were readmitted within 3 months after discharge. There were prognostic relationships between IV diuretic usage and both duration of hospitalization and in-hospital mortality. On multivariable analysis, the time of maximum dose had the biggest impact on outcomes. Duration of hospitalization was prolonged and in-hospital mortality rates increased when the time of maximum dose was delayed. There was little correlation between IV diuretic use and readmission following discharge. Conclusions: Short-term outcomes (duration of hospitalization, in-hospital mortality) correlated with the time of maximum IV diuretic dose; thus, early initiation and subsequent modification of appropriate congestion treatment is critical for prognostic improvement., Competing Interests: Y.S. is affiliated with an endowed department that is supported by Medtronic Japan Co., Ltd. and BIOTRONIK JAPAN Co., Ltd., and has received lecture fees from Otsuka Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Novartis Pharma Co., Ltd., and AstraZeneca Co., Ltd. Y.K., M.M., and H.M. are employees of Otsuka Pharmaceutical Co., Ltd., (Copyright © 2023, THE JAPANESE CIRCULATION SOCIETY.)

The oscillation of shelled microbubbles during exposure to ultrasound is influenced by the mechanical properties of the shell components. The oscillation behavior of bubbles coated with various phospholipids and other amphiphiles has been studied. However, there have been few investigations of how the adsorption conditions of the shell molecules relate to the viscoelastic properties of the shell and influence the oscillation behavior of the bubbles. In the present study, we investigated the oscillation characteristics of microbubbles coated with a poloxamer surfactant, that is, Pluronic F-68, at several concentrations after the adsorption kinetics of the surfactant at the gas-water interface had reached equilibrium. The dilatational viscoelasticity of the shell during exposure to ultrasound was analyzed in the frequency domain from the attenuation characteristics of the acoustic pulses propagated in the bubble suspension. At Pluronic F-68 concentrations lower than 2.0 × 10 -2 mol L -1 , the attenuation characteristics typically exhibited a sharp peak. At concentrations higher than 2.0 × 10 -2 mol L -1 , the peak flattened. The dilatational elasticity and viscosity of the shell were estimated by fitting the theoretical model to the experimental values, which revealed that both the elasticity and viscosity increased markedly at approximately 2.0 × 10 -2 mol L -1 . This suggests that the adsorption properties of Pluronic F-68 strongly affect the oscillation characteristics of microbubbles of a size suitable for medical ultrasound diagnostics.

In the pharmaceutical field, a technique to level the surface of powdered medicines is important in the dispensing process because the flatness of the powder surface affects the packaging accuracy directly. This paper investigates a method for leveling of the surface profile of powder using ultrasound vibration on a plate. The system used comprises a V-shaped plate and two ultrasound transducers, and the plate configuration required was determined from the results of simulations performed by finite element analysis. The resonant longitudinal vibration of the transducers generated the resonant flexural vibration mode of the plate at 27.4 kHz, which resulted in transportation and leveling of the powder. The powder was aggregated at the nodal positions of the flexural standing wave, and a correlation was observed between the sound pressure distribution over the plate and the surface profile of the powder. The powder leveling accuracy was investigated by varying the driving phase difference between the transducers, and it was found that a smaller standing wave ratio for the flexural vibration produced higher leveling accuracy. When the input voltage to the transducers was increased, the leveling time decreased and the leveling accuracy improved; the highest leveling accuracy obtained was 2.2 mm at 130 V pp ., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Daisuke Koyama reports financial support was provided by Japan Science and Technology Agency., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to objectively evaluate the water-jet-functioned electrosurgical knife injection performances in a desktop experiment., Methods: Five types of water-jet-functioned electrosurgical knives, including two injection styles of sheath-type (A: DualKnife J, KD-655L; B: FlushKnife, DK2620-J-B20S; C: Splash M-Knife, DN-D2718B; D: ISSEN, SN1650-20) and tip-type (E: ORISE ProKnife, M00519361) were evaluated. These knives were compared with an injection needle (Control: SuperGrip 25G) as a control. The injection speed under constant pressure and the injection efficiency for each knife against prepared porcine stomach mucosa were evaluated. The additional clear gel injections using an injection needle were observed using an indigo blue-colored gel to evaluate the difference between the locations of water-jet holes., Results: Four types of knives, except for A, showed significantly higher water-jet speeds (A: 0.79 ± 0.03 g/20 s, B: 2.56 ± 0.05 g/20 s, C: 3.09 ± 0.06 g/20 s, D: 2.86 ± 0.05 g/20 s, and E: 1.79 ± 0.03 g/20 s) compared to that of the control (1.21 ± 0.03 g/20 s). Meanwhile, significantly higher efficacy of injection was found in the tip-type water-jet function knife, second to the injection needle (Control: 37.2% ± 35.5%, A: 20.9% ± 20.2%, B: 1.1% ± 2.2%, C: 6.2% ± 12.6%, D: 12.5% ± 15.6%, and E: 33.3% ± 32.2%). An additional injection experiment revealed that the injection with a piercing tip into the gel could achieve sufficient additional injection inside the stacked clear gel., Conclusions: The tip-type water-jet function electrosurgical knife is preferable for effective submucosal injection during endoscopic treatments., Competing Interests: MF received a research grant from Fujifilm Corporation, HOYA Corporation, and Olympus Corporation and a lecture honoraria from Fujifilm Corporation and Olympus Corporation outside the submitted work., (© 2022 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Introduction: Treatment continuation is essential for relapse prevention in patients with schizophrenia. The aim of this exploratory study was to compare the time to treatment discontinuation between patients with schizophrenia prescribed brexpiprazole (BRX group) and those prescribed other atypical antipsychotics (OAA group) in clinical settings in Japan using health insurance claims data., Methods: De-identified data of working individuals with schizophrenia aged < 75 years and their dependents were assessed from April 2017 to May 2020 using a nationwide claims database. Cox proportional hazards models, adjusted for baseline patient variables, were used to compare the time to treatment discontinuation (primary outcome) for 180 days between BRX and OAA groups and to estimate the hazard ratio (HR) with 95% confidence interval (CI). The cumulative treatment continuation rates at 180 days were also estimated. Sensitivity and subgroup analyses were conducted for the primary outcome., Results: The analysis included 978 and 4898 patients in the BRX and OAA groups, respectively. Patients in the BRX group were significantly less likely to discontinue treatment than those in the OAA group (HR 0.86, 95% CI 0.78-0.95; p = 0.0024). The cumulative treatment continuation rates were higher in the BRX group (45.9%, 95% CI 42.5-49.2]) than in the OAA group (39.5%, 95% CI 38.1-41.0; log-rank test, p < 0.0001). Based on patients matched by propensity score, the BRX group was significantly less likely to discontinue treatment than the OAA group (log-rank test, p = 0.0466). Similar results were obtained in sensitivity and subgroup analyses., Conclusion: This real-world study showed that patients in the BRX group were less likely to discontinue treatments than those in the OAA group. These findings suggest that BRX may contribute to treatment continuation among patients with schizophrenia., Trial Registration: University hospital Medical Information Network (UMIN) Clinical Trials Registry: UMIN000044682., (© 2022. The Author(s).)

Objectives: To evaluate factors to predict overall survival of metastatic urothelial carcinoma patients treated with gemcitabine plus cisplatin chemotherapy or pembrolizumab therapy., Methods: We retrospectively evaluated two metastatic urothelial carcinoma cohorts treated with (i) gemcitabine plus cisplatin or (ii) pembrolizumab. The gemcitabine plus cisplatin cohort was treated from December 2005 through December 2014 while the pembrolizumab cohort was treated from January 2018 through December 2020. Using multivariate analyses, we evaluated the risk factors for overall survival in each cohort and compared them. None of the gemcitabine plus cisplatin cohort patients were treated with pembrolizumab. All patients in the pembrolizumab cohort were treated with prior platinum-based chemotherapy., Results: There were 184 patients in the gemcitabine plus cisplatin cohort and 91 in the pembrolizumab cohort. The mean follow-up periods were 714 and 284 days, respectively. In multivariate analysis, the risk factors for overall survival in the gemcitabine plus cisplatin cohort were liver metastasis, worse Eastern Cooperative Oncology Group performance status (1 or more), no primary site resection, and a high prognostic index (1 or more). In the pembrolizumab cohort, liver metastasis, bone metastasis, and worse Eastern Cooperative Oncology Group-performance status (1 or more), and high prognostic index (1 or more) were the risk factors for overall survival. In the pembrolizumab cohort, patients with a complete response or partial response during prior platinum-based chemotherapy had better overall survival with the following pembrolizumab treatment than those with stable or progressive disease (P = 0.004)., Conclusions: Considering the similarity of these risk factors in two sequential treatments, it may be possible to predict the response to pembrolizumab according to the response to prior chemotherapy., (© 2022 The Japanese Urological Association.)

A varifocal concave-convex lens using ultrasound and transparent viscoelastic gel is reported. The configuration of the lens is simple and thin, consisting of four pieces of a piezoelectric ultrasound transducer, a glass disk, and a transparent silicone gel film. It uses a combination of the ultrasound resonant flexural standing- and traveling-wave modes excited by in-phase and four-phase drives so that the lens can change its shape to both concave and convex by switching the resonance mode with the same structure. The acoustic radiation force (ARF) originated from the resonant flexural vibration modes changed the surface profile of the gel. Convex and concave deformation were generated at the center of the lens at the resonance frequencies of 38 and 60 kHz, respectively, indicating that a varifocal concave-convex lens could be fabricated by controlling the driving frequency, voltage amplitude, and phase differences among the ultrasound transducers. The deformational displacement on the lens surface and the change in the focal length increased with the input voltage amplitude. The optical microscopic images observed through the lens were enlarged 1.28× (reduced 0.92× ) in the convex (concave) mode with 20 [Formula: see text]. The response time for focusing and the temperature stability under operation were evaluated. By switching the resonance vibration modes of the lens through the input signals to multiple ultrasound transducers, the variable-focus function with both concave and convex lenses was achieved in the same configuration.

For simple, safe, portable, and inexpensive evaluation suitable for leg bone diseases of racehorses in the field, an ultrasonic measurement technique was applied to evaluate wave velocities. A digital model of the third metacarpal bone with the bucked shin was fabricated using high-resolution peripheral quantitative computerized tomography data of a racehorse. This model was anisotropic and heterogeneous, and was constructed using the measured ultrasonic wave velocities in the bone. With this model, ultrasonic wave propagation along the bone axis was simulated using the elastic finite-difference time-domain method. We found two main waves with different propagation velocities. The fast-waves showed a wave velocity close to the longitudinal wave in the axial direction. However, the apparent velocities changed dramatically owing to bone surface irregularities (changes of the shape) in the area of bucked shin. The slow-waves showed a wave velocity close to the shear wave, which was unaffected by the bone surface irregularities. The simple comparison of different wave behaviors may be a suitable parameter for the initial in vivo screening of bucked shin in the legs of racehorses, which can be performed in the field.

Background: In recent years, transthyretin amyloid cardiomyopathy (ATTR-CM) has received increasing attention; however, the epidemiology of ATTR-CM in Japan is not yet understood. In the Kumamoto Cardiac Amyloid Survey, we evaluated the current incidence, clinical characteristics, diagnostic approaches, and treatment strategies for ATTR-CM and compared tafamidis-prescription hospitals with regional hospitals., Methods: We conducted a retrospective multicenter observational cohort study. The registry included patients with ATTR-CM diagnosed in two tafamidis-prescription hospital institutes [Japanese Circulation Society (JCS)-certified facilities] and 15 regional cardiovascular facilities in Kumamoto between January 2018 and December 2020., Results: In total, 174 patients were diagnosed with ATTR-CM. The incidence of ATTR-CM was estimated to be approximately 1 per 10,000 person-years in the elderly population (>65 years old) in Kumamoto. Compared with that in the JCS-certified facilities cohort (n=115), age at diagnosis was significantly older (84.5 ± 5.6 vs. 77.5 ± 6.3 years old; p<0.01) in the regional hospitals cohort (n=59). Histological (25% vs. 81%; p<0.01) and genetic diagnosis (7% vs. 82%) were also less frequently performed. Probable (as indicated by positive bone scintigraphy findings with confirmation of monoclonal protein absence) and possible (as indicated by positive bone scintigraphy findings without confirmation of monoclonal protein absence) ATTR-CM accounted for the majority of cases (75% vs. 19%; p<0.01) in the regional hospitals cohort compared to the JCS-certified facilities cohort. There were no cases of hereditary ATTR-CM among the patients who underwent TTR genetic testing (n=98)., Conclusions: We confirmed the incidence of ATTR-CM in Kumamoto and the diagnostic approach used in patients with ATTR-CM. Further prospective studies with a larger sample are needed to validate our results and to further shed light on the epidemiology of ATTR-CM in Japan., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest, (Copyright © 2022. Published by Elsevier Ltd.)

A pump-probe system with a subnanosecond pulsed laser is expected to be a compact and inexpensive transient spectroscopic system that enables nondestructive and noncontact evaluations of the physical properties. However, an improvement in the sensitivity and a theoretical model to complement the measurement signal are necessary to obtain the transient signal precisely because of the low sensitivity and large time resolution. We have developed a highly sensitive pump-probe system with a subnanosecond pulsed laser that combines signal amplification based on surface plasmon resonance (SPR) in this study. An integrated theoretical model of the transient response obtained by a subnanosecond pump-probe under the SPR condition was proposed. Our model consisted of the profile descriptions of the used pulse source, temperature change, generated thermoelastic stress, estimated permittivity change in the metal film, and estimated reflectivity change. The theoretical estimations in the time domain and the incident angle dependence were compared with those of the experimental results to verify our theory. As a result, the estimations were well in agreement with the experimental results. Moreover, the signal-amplification mechanism based on SPR was discussed using our theory. The amplification was caused by the broadening of the resonant curve of SPR and the shift of the resonant angle, which seemed to come from the increase in the electron-phonon scattering rate and the thermal expansion of the metal film, respectively. A clear mechanism of SPR-based signal amplification of the subnanosecond pump-probe was identified through experimental and theoretical approaches.

Rodents acquire more information from the sense of smell than humans because they have a nearly fourfold greater variety of olfactory receptors. They use olfactory information not only for obtaining food, but also for detecting environmental dangers. Predator-derived odor compounds provoke instinctive fear and stress reactions in animals. Inbred lines of experimental animals react in an innate stereotypical manner to predators even without prior exposure. Predator odors have also been used in models of various neuropsychiatric disorders, including post-traumatic stress disorder following a life-threatening event. Although several brain regions have been reported to be involved in predator odor-induced stress responses, in this mini review, we focus on the functional role of inhibitory neural circuits, especially in the anterior piriform cortex (APC). We also discuss the changes in these neural circuits following innate reactions to odor exposure. Furthermore, based on the three types of modulation of the stress response observed by our group using the synthetic fox odorant 2,5-dihydro-2,4,5-trimethylthiazoline, we describe how the APC interacts with other brain regions to regulate the stress response. Finally, we discuss the potential therapeutic application of odors in the treatment of stress-related disorders. A clearer understanding of the odor-stress response is needed to allow targeted modulation of the monoaminergic system and of the intracerebral inhibitory networks. It would be improved the quality of life of those who have stress-related conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Matsukawa, Yoshikawa, Katsuyama, Aizawa and Sato.)

Odors trigger various emotional responses such as fear of predator odors, aversion to disease or cancer odors, attraction to male/female odors, and appetitive behavior to delicious food odors. Odor information processing for fine odor discrimination, however, has remained difficult to address. The olfaction and color vision share common features that G protein-coupled receptors are the remote sensors. As different orange colors can be discriminated by distinct intensity ratios of elemental colors, such as yellow and red, odors are likely perceived as multiple elemental odors hierarchically that the intensities of elemental odors are in order of dominance. For example, in a mixture of rose and fox-unique predator odors, robust rose odor alleviates the fear of mice to predator odors. Moreover, although occult blood odor is stronger than bladder cancer-characteristic odor in urine samples, sniffer mice can discriminate bladder cancer odor in occult blood-positive urine samples. In forced-choice odor discrimination tasks for pairs of enantiomers or pairs of body odors vs. cancer-induced body odor disorders, sniffer mice discriminated against learned olfactory cues in a wide range of concentrations, where correct choice rates decreased in the Fechner's law, as perceptual ambiguity increased. In this mini-review, we summarize the current knowledge of how the olfactory system encodes and hierarchically decodes multiple elemental odors to control odor-driven behaviors., Competing Interests: The authors declare that this study received research budget from Sumitomo Chemical Co., Ltd, which was used for SPME-GC-MS measurements. This study received funding from Japan Tobacco INC. The funder had the following involvement in the study: Shared features of odor coding between humans and mice., (Copyright © 2022 Sato, Matsukawa, Iijima and Mizutani.)

Genetic counselors routinely assess and understand clients' needs at the beginning of a session. Attending a genetic counseling session with or without companions is an objective sign that genetic counselors can easily notice. This study focused on clients' reasons for their accompaniment status for genetic counseling, which we categorize into attending with or without a companion(s). A questionnaire survey and interviews were conducted using snowball sampling, starting with the chief executive officer (CEO) of the Japanese hereditary breast and ovarian cancer (HBOC) support group. Of 32 participants, 19 continued with an in-depth interview after answering the questionnaire. Five themes were identified from the interview: (1) personal confidence, (2) decision-making style, (3) family members' habits and time availability, (4) considerations and conflicts with family members, and (5) healthcare provider's suggestion. Our data suggested that the clients expected their companion(s) to play certain roles. This indicates that the reasons of accompaniment status will be helpful for genetic counselors to understand both clients' and their families' motivations, personalities, habits, and psychosocial backgrounds. In a high-context culture such as that of Japan, accompaniment status may be a helpful sign to understand clients' true worries. In addition, some companions may be future clients in genetic counseling, due to the genetic nature of the disease. In conclusion, our study indicated that it is important for genetic counselors to record accompaniment status before the initial genetic counseling and to pay attention to its reasons at the beginning of the session, which may lead them to understand the client's psychosocial background to facilitate better client-centered genetic counseling., (© 2021 National Society of Genetic Counselors.)

Objective: Cytological diagnosis of pancreatic specimens obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is often challenging because of the small sample size or well-differentiated adenocarcinoma with weak cytological atypia. Therefore, the sensitivity and specificity of cytological diagnosis for pancreatic cancer should be improved. Hence, we aimed to clarify the utility of cytological scoring to distinguish malignant from benign lesions for cytological diagnosis of pancreatic EUS-FNA specimens., Methods: Seven reviewers, including four cytotechnologists and three medical doctors, evaluated 20 morphological indices in pancreatic specimens obtained by EUS-FNA (malignant, n = 111; benign, n = 31). Statistical analyses were performed using Fisher's exact test, logistic regression analysis, the area under the receiver operating characteristic curve, and Youden index., Results: Among the 20 indices, there was a high incidence rate (>40%) of the following 13 indices in malignant cases: irregular structure, hyperchromatic nucleus, irregular cell polarity, unclear cell boundaries, nuclear membrane thickening, anisonucleosis, overlapping, irregular nuclei, high nuclear-cytoplasmic ratio, binding decline, the simultaneous appearance of malignant and benign cells, enlarged nucleoli, and background necrosis. When we diagnosed pancreatic specimens using these 13 cytological indices, the cut-off value of 8/9 showed the highest Youden index (0.950) as well as high sensitivity and specificity in distinguishing malignant from benign specimens (98% and 97%, respectively)., Conclusion: Thirteen cytological indices showed high sensitivity and specificity in differentiating malignant and benign lesions using pancreatic EUS-FNA samples. All 13 indices were important for diagnosing malignancy in the pancreatic cytology smear of EUS-FNA. Further validation studies are required., (© 2021 John Wiley & Sons Ltd.)