Publications by authors named "Hiroyuki Tanaka"

1,089 Publications

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Reliability and Validation of the Japanese Version of the Patient Empowerment Scale.

Healthcare (Basel) 2022 Jun 20;10(6). Epub 2022 Jun 20.

Graduate School of Comprehensive Rehabilitation, Osaka Prefecture University, Habikino-shi 583-8555, Japan.

Empowerment scales for inpatients have been developed worldwide, but their validity and reliability have not been adequately tested and applied to the health promotion and care among older adults during hospitalization. In this study, the Patient Empowerment Scale developed by Faulkner was translated into Japanese, and Japanese patients were surveyed to test its clinical applicability. To test its applicability, 151 patients in rehabilitation wards were surveyed in four municipalities. After considering ceiling/floor effects and validating the structure, the Patient Empowerment Scale-Japanese comprised 37 items and six factors: subject-staff interaction, environmental adjustment through collaboration, necessary information gathering and problem awareness, proactive behavioral practices, self-disclosure, and self-management of activities. Criteria-related validity assessment confirmed the scale's correlation with the Health Locus of Control Scale, General Self-Efficacy Scale, 13-item Sense of Coherence Scale, Rosenberg Self-Esteem Scale, and Philadelphia Geriatric Center Morale Scale. Regarding internal consistency, the Cronbach's alpha was 0.93 for all 37 items. The Cronbach's alphas for the six factors were 0.93, 0.91, 0.92, 0.92, 0.91, and 0.75, respectively. In our test/re-test of reliability, Spearman's rank correlation coefficient between the first and second total scores was ρ = 0.96, < 0.01. These results confirm the scale's validity and reliability, and its applicability to older hospitalized patients.
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http://dx.doi.org/10.3390/healthcare10061151DOI Listing
June 2022

Course of Cardiac Magnetic Resonance Imaging Findings in Acute Myocarditis after COVID-19 mRNA Vaccination.

Intern Med 2022 Jun 21. Epub 2022 Jun 21.

Department of Cardiology, Tokyo Metropolitan Tama Medical Center, Japan.

Myocarditis is being increasingly reported as a rare complication of coronavirus disease 2019 (COVID-19) mRNA vaccines. We herein report a case of myocarditis following COVID-19 mRNA vaccination in a man. Cardiac magnetic resonance imaging (CMRI) revealed an area of high signal intensity on short T1 inversion recovery (STIR) and late gadolinium enhancement (LGE), which are characteristic of myocarditis. Follow-up CMRI performed six months later revealed improvement in the myocardial edema and LGE findings. CMRI is a useful non-invasive imaging modality for making an initial diagnosis as well as for follow-up in cases of myocarditis after COVID-19 mRNA vaccination.
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http://dx.doi.org/10.2169/internalmedicine.9797-22DOI Listing
June 2022

Development of Pure Green Thermally Activated Delayed Fluorescence Material by Cyano Substitution.

Adv Mater 2022 Jun 20:e2201778. Epub 2022 Jun 20.

Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.

Multiple resonance (MR) effect-induced thermally activated delayed fluorescence (TADF) materials have garnered significant attention because they can achieve both high color purity and high external quantum efficiency (EQE). However, the reported green-emitting MR-TADF materials exhibit broader emission compared to those of blue-emitting ones and suffer from severe efficiency roll-off due to insufficient rate constants of reverse intersystem crossing process (k ). Herein, we report a pure green MR-TADF material (ν-DABNA-CN-Me) with high k of 10 s . The key to success is introduction of cyano groups into a blue-emitting MR-TADF material (ν-DABNA), which causes remarkable bathochromic shift without a loss of color purity. The organic light-emitting diode employing it as an emitter exhibits green emission at 504 nm with a small full-width at half-maximum of 23 nm, corresponding to the Commission Internationale d'Éclairage coordinates of (0.13, 0.65). The device achieves a high maximum EQE of 31.9% and successfully suppresses the efficiency roll-off at a high luminance. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adma.202201778DOI Listing
June 2022

Wireless muometric navigation system.

Sci Rep 2022 Jun 16;12(1):10114. Epub 2022 Jun 16.

University of Tokyo, Tokyo, Japan.

While satellite-based global navigation systems have become essential tools in our daily lives, their effectiveness is often hampered by the fact that the signals cannot be accessed in underground, indoor, or underwater environments. Recently, a novel navigation system has been invented to address this issue by utilizing the characteristics of the ubiquitous and highly penetrative cosmic-ray muons. This technique, muometric navigation, does not require active signal generation and enables positioning in the aforementioned environments within a reference coordinate defined by the three-dimensional positions of multiple detectors. In its first phase of development, these reference detectors had to be connected to the receivers via a wired configuration to guarantee precise time synchronization. This work describes more versatile, wireless muometric navigation system (MuWNS), which was designed in conjunction with a cost-effective, crystal-oscillator-based grandmaster clock and a performance evaluation is reported for shallow underground/indoor, deep underground and undersea environments. It was confirmed that MuWNS offers a navigation quality almost equivalent to aboveground GPS-based handheld navigation by determining the distance between the reference frame and the receivers within a precision range between 1 and 10 m.
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http://dx.doi.org/10.1038/s41598-022-13280-4DOI Listing
June 2022

Whole-genome sequencing analysis and protocol for RNA interference of the endoparasitoid wasp Asobara japonica.

DNA Res 2022 Jun 10. Epub 2022 Jun 10.

Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, 305-8577, Japan.

Asobara japonica is an endoparasitic wasp that parasitizes Drosophila flies. It synthesizes various toxic components in the venom gland and injects them into host larvae during oviposition. To identify and characterize these toxic components for enabling parasitism, we performed the whole-genome sequencing (WGS) and devised a protocol for RNA interference (RNAi) with A. japonica. Because it has a parthenogenetic lineage due to Wolbachia infection, we generated a clonal strain from a single wasp to obtain highly homogenous genomic DNA. The WGS analysis revealed that the estimated genome size was 322 Mb with a heterozygosity of 0.132%. We also performed RNA-seq analyses for gene annotation. Based on the qualified WGS platform, we cloned ebony-Aj, which encodes the enzyme N-β-alanyl dopamine synthetase (NBAD), which is involved in melanin production. The microinjection of double-stranded RNA targeting ebony-Aj led to body color changes in adult wasps, phenocopying ebony-Dm mutants. Furthermore, we identified putative venom genes as a target of RNAi, confirming that dsRNA injection-based RNAi specifically suppressed the expression of the target gene in wasp adults. Taken together, our results provide a powerful genetic toolkit for studying the molecular mechanisms of parasitism.
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http://dx.doi.org/10.1093/dnares/dsac019DOI Listing
June 2022

Procedural results and in-hospital outcomes of percutaneous coronary intervention for chronic total occlusion in patients with reduced left ventricular ejection fraction: Sub-analysis of the Japanese CTO-PCI Expert Registry.

Catheter Cardiovasc Interv 2022 Jun 1. Epub 2022 Jun 1.

Japanese CTO-PCI Expert Foundation, Kurashiki, Japan.

Objectives: To evaluate the procedural results and in-hospital outcomes of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) in patients with reduced left ventricular ejection fraction (LVEF).

Background: While the technical success of general CTO-PCI has improved, CTO-PCI patients with reduced LVEF remain at high-risk for adverse events.

Methods: The data of 820 patients with LVEF ≤ 35% (Group 1), 1816 patients with LVEF = 35%-50% (Group 2), and 5503 patients with LVEF ≥ 50% (Group 3), registered in the Japanese CTO-PCI Expert Registry from January 2014 to December 2019, were retrospectively analyzed. The primary endpoint was in-hospital major adverse cardiac or cerebrovascular events (MACCEs), including death, myocardial infarction, stent thrombosis, stroke, and emergent revascularization. Secondary endpoints included procedural details, guidewire success, and technical success.

Results: There were no differences in guidewire and technical success rates between the groups. In-hospital MACCEs was significantly higher in Group 1 (Group 1 vs. Group 2 vs. Group 3: 3.4% vs. 1.7% vs. 1.5%, p = 0.001) and was especially driven by death (1.3% vs. 0.3% vs. 0.1%, p < 0.001) and stroke (0.7% vs. 0.2% vs. 0.2%, p = 0.007). Multivariate analysis showed that LVEF ≤ 35% (odds ratio [OR]; 1.58, 95% confidence interval [CI]; 1.04-2.41, p = 0.03) and New York Heart Association (NYHA) class ≥ 3 (OR; 2.01, 95% CI; 1.03-3.93, p = 0.04) were predictors of in-hospital MACCEs.

Conclusions: In-hospital MACCEs were significantly higher in patients with LVEF ≤ 35%. LVEF ≤;35% and NYHA class ≥ 3 were predictors of in-hospital MACCEs after CTO-PCI.
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http://dx.doi.org/10.1002/ccd.30231DOI Listing
June 2022

Singing Is a Risk Factor for Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Case-Control Study of Karaoke-Related Coronavirus Disease 2019 Outbreaks in 2 Cities in Hokkaido, Japan, Linked by Whole Genome Analysis.

Open Forum Infect Dis 2022 May 23;9(5):ofac158. Epub 2022 Mar 23.

Center for Surveillance, Immunization and Epidemiologic Research, National Institute of Infectious Diseases, Tokyo, Japan.

Background: Singing in an indoor space may increase the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a case-control study of karaoke-related coronavirus disease 2019 (COVID-19) outbreaks to reveal the risk factors for SARS-CoV-2 infection among individuals who participate in karaoke.

Methods: Cases were defined as people who enjoyed karaoke at a bar and who tested positive for SARS-CoV-2 by reverse-transcription polymerase chain reaction between 16 May and 3 July 2020. Controls were defined as people who enjoyed karaoke at the same bar during the same period as the cases and tested negative. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. ORs of key variables adjusted for each other were also estimated (aOR).

Results: We identified 81 cases, the majority of whom were active elderly individuals (median age, 75 years). Six cases died (case fatality ratio, 7%). Among the cases, 68 (84%) were guests, 18 of whom had visited ≧2 karaoke bars. A genome analysis conducted in 30 cases showed 6 types of isolates within 4 single-nucleotide variation difference. The case-control study revealed that singing (aOR, 11.0 [95% CI, 1.2-101.0]), not wearing a mask (aOR, 3.7 [95% CI, 1.2-11.2]), and additional hour spent per visit (aOR, 1.7 [95% CI, 1.1-2.7]) were associated with COVID-19 infection.

Conclusions: A karaoke-related COVID-19 outbreak that occurred in 2 different cities was confirmed by the results of genome analysis. Singing in less-ventilated, indoor and crowded environments increases the risk of acquiring SARS-CoV-2 infection. Wearing a mask and staying for only a short time can reduce the risk of infection during karaoke.
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http://dx.doi.org/10.1093/ofid/ofac158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992236PMC
May 2022

Activated carbon-based immunochromatographic strip test for the rapid qualitative analysis of swertiamarin and sweroside.

J AOAC Int 2022 May 6. Epub 2022 May 6.

Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan.

Background: Swertia japonica (S. japonica) is a medicinal plant that belongs to the Gentianaceae family. Several reports confirm the biological effects of the S. japonica extract. This plant is mainly used as a digestive stimulant, appetite stimulant, and gastrointestinal disease remedy in Japan. Secoiridoid glycosides are a group of compounds related to the beneficial effects of this plant.

Objective: We developed an immunochromatographic strip test for major secoiridoid glycosides, such as swertiamarin (SM) and sweroside (SS) detection.

Method: We fabricated an immunoprobe using activated carbon as a reporter molecule and a monoclonal antibody against SM and SS (MAb D2) as a detection molecule. The test and control zones of the strip test contained SM-cBSA and Goat pAb anti-mouse IgM HRP conjugate, respectively. The immunoprobe reacted competitively with free SM and/or SS and immobilized SM-cBSA. The results were read and interpreted by the black spot intensity in the test zone.

Results: We succeeded in developing a strip test system with a detection limit (LOD) of 12.5 µg/mL. The selectivity and reliability evaluation revealed that the strip test is suitable for detecting SM and SS in S. japonica. The result was ready to be read in 30 min.

Conclusion And Highlights: To the best of our knowledge, this is the first immunochromatographic strip test developed for the detection of SM and SS in S. japonica samples. This method can be a useful tool for the screening of biologically active S. japonica samples for further preparation of traditional medicine.
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http://dx.doi.org/10.1093/jaoacint/qsac054DOI Listing
May 2022

Cosmic time synchronizer (CTS) for wireless and precise time synchronization using extended air showers.

Sci Rep 2022 Apr 30;12(1):7078. Epub 2022 Apr 30.

University of Tokyo, Tokyo, Japan.

Precise time synchronization is an essential technique required for financial transaction systems, industrial automation and control systems, as well as land and ocean observation networks. However, the time synchronization signals based on the global-positioning-system (GPS), or global-navigation-satellite-system, are sometimes unavailable or only partially available in indoor, underground and underwater environments. In this work, the simultaneous and penetrative natures of the muon component of the extended air shower (EAS) were used as signals for time synchronization in environments with little or no GPS coverage. CTS was modeled by combining the results of previous EAS experiments with OCXO holdover precision measurements. The results have shown the capability of CTS to reach perpetual local time synchronization levels of less than 100 ns with a hypothetical detector areal coverage of larger than 2 × 10. We anticipate this level of areal coverage is attainable and cost-effective for use in consumer smartphone networks and dense underwater sensor networks.
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http://dx.doi.org/10.1038/s41598-022-11104-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9056511PMC
April 2022

Aberrant Expression of Cardiac Troponin-T in Lung Cancer Tissues in Association With Pathological Severity.

Front Cardiovasc Med 2022 11;9:833649. Epub 2022 Apr 11.

Division of Cardiovascular Medicine and Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

Background: Cardiac troponin-T () is exclusively present in cardiac muscle. Measurement of is used for diagnosing acute coronary syndrome. However, its expression may not be limited in myocardium. This study aimed at evaluating the expression of in neoplastic tissues.

Methods And Results: We used paraffin-embedded blocks of 68 patients with lung cancer (age, 68 ± 11 years old; early-stage, 33; advance-stage, 35) at Miyazaki University Hospital, Japan between January 1, 2017, and March 31, 2019. We stained the slide sections with primary monoclonal antibody against protein, and assessed the frequency of positive staining, and its association with pathological severity. In addition, we examined whether gene is detected in lung cancer tissues of four patients using reverse transcription-polymerase chain reaction. Immunoreactivity for protein was present in the cytoplasm and nucleus of lung cancer cells. The frequency was 37% (25 of 68) in all patients and was irrespective of histologic type (six of 13, squamous cell carcinoma; 18 of 50, adenocarcinoma; 0 of 4, neuroendocrine cell carcinoma; 1 of 1, large cell carcinoma). The prevalence increased with pathological staging [9% (3 of 33) at early-stage (Stage 0-I); 63% (22 of 35) at advance-stage (Stage II-IV and recurrence)]. In addition, frequency of positive staining for increased with pleural (χ = 5.877, = 0.015) and vascular (χ = 2.449, = 0.118) invasions but decreased with lymphatic invasion (χ = 3.288, = 0.070) in specimens performed surgical resection. Furthermore, mRNA was detected in the resected squamous cell carcinoma and adenocarcinoma tissues.

Conclusions: Our data suggest the aberrant expression of in lung cancer and its prevalence increases with pathological severity.
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http://dx.doi.org/10.3389/fcvm.2022.833649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037982PMC
April 2022

Muography for a dense tide monitoring network.

Sci Rep 2022 04 25;12(1):6725. Epub 2022 Apr 25.

University of Tokyo, Tokyo, Japan.

Sub-hourly to seasonal and interannual oceanographic phenomena can be better understood with high special resolution and high frequency tidal observations. However, while current tidal measurements can provide sufficiently high observational density in terms of time, the observational density in terms of space is low mainly due to the high expense of constructing tide gauge stations. In this work, we designed a novel tide monitoring technique with muography that could be operated in near-shore basements (or similar structures on land below sea level) and found that more practical, stable, robust and cost-effective high-spatiotemporal-density tide measurements are possible. Although the time resolution, sensitivity, and the distance between the detectors and the shorelines are tradeoffs, hourly and annual sensitivity (ability to detect the tide height variations) of less than 10 cm and 1 mm can be statistically attained, respectively. It is anticipated that the current muographic technique could be applied as an alternative, cost-effective and convenient dense tidal monitor network strategy in coastal areas worldwide.
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http://dx.doi.org/10.1038/s41598-022-10373-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039059PMC
April 2022

Longitudinal changes in an autonomously functioning thyroid nodule with coexisting follicular thyroid carcinoma over 14 years.

Oxf Med Case Reports 2022 Apr 19;2022(4):omac041. Epub 2022 Apr 19.

Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

We present a female patient with autonomously functioning thyroid nodule (AFTN) and coexisting follicular thyroid carcinoma (FTC). At age 21, a left thyroid nodule was incidentally detected on computer tomography (CT) scan. At age 33, she had cervical compression and CT showed the left thyroid nodule had increased in size from 13 to 27 mm. Laboratory investigation showed subclinical hyperthyroidism with positive for anti-thyroid peroxidase antibody and normal level of serum thyroglobulin. Repeated fine needle aspiration cytology diagnosed with follicular neoplasm with Hashimoto's thyroiditis. At age 35, she presented with palpitations due to overt hyperthyroidism. The left thyroid nodule increased in diameter to 33 mm, and thyroid scintigraphy showed elevated uptake in the left thyroid nodule, indicating an AFTN. Thyroidectomy was performed, and the left thyroid nodule was pathologically diagnosed with FTC with capsular invasion. In this case, the longitudinal increase in AFTN size suggested FTC and led to thyroidectomy.
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http://dx.doi.org/10.1093/omcr/omac041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021971PMC
April 2022

Clinical utility of an assessment scale for engagement in activities for patients with moderate-to-severe dementia: additional analysis.

Psychogeriatrics 2022 Apr 17. Epub 2022 Apr 17.

Osaka Metropolitan University Graduate School of Rehabilitation Science, Habikino, Japan.

Background: We developed the assessment scale for engagement in activities (ASEA), an assessment tool used to quantify engagement in therapeutic activities for patients with moderate-to-severe dementia. In this study, we report additional analyses to confirm the viability of ASEA as a reliable measurement scale.

Methods: This study included 195 patients with moderate-to-severe dementia in a psychiatric acute-phase hospital. Additional analyses based on the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist were as follows: (i) exploratory and confirmatory factor analysis; (ii) standard error of measurement (SEM), minimal detectable change (MDC) and limit of agreement (LOA); (iii) short change score from baseline to 2 weeks; and (iv) correlation to the facial expression analysis system.

Results: Exploratory factor analysis yielded two factors. This two-factor model of ASEA exhibited an acceptable and validated model fit (comparative fit index = 0.954, Tucker Lewis index = 0.936, goodness-of-fit index = 0.927, adjusted goodness-of-fit index = 0.873, root mean square error of approximation = 0.091, standardised root mean square residual = 0.045) by confirmatory factor analysis. SEM and MDC were 1.29 and 3.80, respectively. The Bland-Altman plot for examining LOA showed no apparent fixed bias. From baseline to 2 weeks later, 129 participants were retested. The mean ASEA total score improved significantly (Wilcoxon signed-rank test; P < 0.01, effect size = 0.25) from baseline (14.30 ± 2.63) to 2 weeks later (15.00 ± 2.73). The correlation between each emotion value was calculated using Kokoro sensor, which is an affect analysis based on human facial expression data using deep learning. For the 36 video data samples, the total score and domains of arousal, interaction, and affect in ASEA were statistically significantly correlated with the emotion value of joy, engagement, and valence (Spearman rank correlation; P < 0.05).

Conclusions: Among the few evaluation methods specific to severe dementia, ASEA is a useful scale for quantifying and evaluating the state of engagement in therapeutic activities.
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http://dx.doi.org/10.1111/psyg.12835DOI Listing
April 2022

Impact of Timing and Treatment Strategy on Coronary Perforation During Percutaneous Coronary Intervention for Chronic Total Occlusion.

Am J Cardiol 2022 Jun 14;172:26-34. Epub 2022 Apr 14.

Toyohashi Heart Centre, Aichi, Japan.

Coronary perforations during chronic total occlusion percutaneous coronary intervention (CTO-PCI) are potential complications and reportedly associated with adverse events. This study aimed to describe the clinical characteristics and timing of perforations during CTO-PCI. Data from the Japanese CTO-PCI expert registry included 8,760 patients who underwent CTO-PCI between January 2014 and January 2019. The major adverse cardiac and cerebrovascular events were defined as death, tamponade, myocardial infarction, stent thrombosis, stroke, and revascularization. The guidewire manipulation time was defined as the time required to cross the CTO without perforation. Among these patients, 333 (3.8%) developed perforation during the CTO crossing attempt. Of the 333 patients, 29 developed cardiac tamponades (8.7%). Perforations more frequently occurred in a retrograde wiring than in an anterograde wiring (6.6% vs 1.7%, p <0.0001). A longer guidewire manipulation time was associated with the occurrence of perforation (median 101 minutes [interquartile range 59 to 150 minutes] in the perforation group vs 54.9 minutes [interquartile range 21.1 to 112.7 minutes] in the nonperforation group, p <0.0001). Risk factors for perforation were age, history of coronary bypass graft, right coronary artery lesion, de novo lesion, use of a stiff guidewire, and guidewire manipulation time of >60 minutes during anterograde wiring and age, non-left anterior descending artery lesion, use of a polymer-jacketed guidewire, and use of epicardial channel during retrograde wiring. In conclusion, risk factors for perforation were different between anterograde and retrograde wirings. A prolonged guidewire manipulation time was associated with the occurrence of perforation, especially during anterograde wiring.
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http://dx.doi.org/10.1016/j.amjcard.2022.02.019DOI Listing
June 2022

Periodic sea-level oscillation in Tokyo Bay detected with the Tokyo-Bay seafloor hyper-kilometric submarine deep detector (TS-HKMSDD).

Sci Rep 2022 04 12;12(1):6097. Epub 2022 Apr 12.

Wigner Research Centre for Physics, Budapest, Hungary.

Meteorological-tsunami-like (or meteotsunami-like) periodic oscillation was muographically detected with the Tokyo-Bay Seafloor Hyper-Kilometric Submarine Deep Detector (TS-HKMSDD) deployed in the underwater highway called the Trans-Tokyo Bay Expressway or Tokyo Bay Aqua-Line (TBAL). It was detected right after the arrival of the 2021 Typhoon-16 that passed through the region 400 km south of the bay. The measured oscillation period and decay time were respectively 3 h and 10 h. These measurements were found to be consistent with previous tide gauge measurements. Meteotsunamis are known to take place in bays and lakes, and the temporal and spatial characteristics of meteotsunamis are similar to seismic tsunamis. However, their generation and propagation mechanisms are not well understood. The current result indicates that a combination of muography and trans-bay or trans-lake underwater tunnels will offer an additional tool to measure meteotsunamis at locations where tide gauges are unavailable.
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http://dx.doi.org/10.1038/s41598-022-10078-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005544PMC
April 2022

Initial Experience of Atezolizumab Plus Bevacizumab for Advanced Hepatocellular Carcinoma in Clinical Practice.

Cancer Diagn Progn 2021 May-Jun;1(2):83-88. Epub 2021 May 3.

Department of Gastroenterology and Hepatology, Fujita Health University, Aichi, Japan.

Background/aim: The aim of this study was to investigate the outcomes of atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma (HCC), including those with disease refractory to lenvatinib, in clinical practice.

Patients And Methods: Of 34 patients treated with atezolizumab plus bevacizumab, a total of 23, including 16 with lenvatinib failure, were enrolled in this retrospective study. The adverse events, changes in liver function and antitumor responses at 6 weeks after starting therapy were evaluated.

Results: The incidence of grade 3 adverse events was low, at 13.0%. Albumin-bilirubin scores did not worsen at 3 and 6 weeks compared to baseline. The objective response rate and disease control rate at 6 weeks were 17.4% and 78.3% according to Response Evaluation Criteria in Solid Tumors (RECIST), and 30.4% and 78.3% according to modified RECIST, respectively.

Conclusion: Our results suggest that atezolizumab plus bevacizumab might have potential therapeutic safety and efficacy in patients with advanced HCC, including those with disease refractory to lenvatinib. Further studies are needed to confirm the outcomes of atezolizumab plus bevacizumab after lenvatinib failure.
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http://dx.doi.org/10.21873/cdp.10012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962759PMC
May 2021

Comparison and Validation of Long-Term Bleeding Events for Academic Bleeding Risk (ARC-HBR) Criteria and Contemporary Risk Scores for Percutaneous Coronary Intervention With a Second-Generation Drug Eluting Stent.

Circ J 2022 Apr 9. Epub 2022 Apr 9.

Department of Cardiovascular Medicine, Kurashiki Central Hospital.

Background: The Academic Research Consortium for High Bleeding Risk (ARC-HBR) defined a consensus clinical criterion for patients at HBR undergoing percutaneous coronary intervention (PCI). This study aimed to validate and compare the ARC-HBR criteria and the contemporary risk score for long-term bleeding outcomes using a cohort of patients undergoing PCI.Methods and Results: This study analyzed 3,410 patients who underwent PCI between 2010 and 2013. The endpoint was defined as incidence of The Bleeding Academic Research Consortium 3 or 5 bleeding events. In addition to ARC-HBR, this study validated the predictability of the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score, Patterns of non-adherence to Anti-platelet Regimens In Stented patients (PARIS) bleeding score, and Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) bleeding scores for bleeding events. There was a trend toward an increase in bleeding events, as the risk score increased for all bleeding risk scores used in this study. The ARC-HBR criteria had higher diagnostic sensitivity for bleeding events than other bleeding risk scores.

Conclusions: Patients with a higher number of risk factors in each of the four bleeding risk scores had a higher risk of long-term bleeding events. In comparison to other contemporary risk scores, the ARC-HBR criteria were more sensitive in the identification of patients with bleeding events in the long-term.
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http://dx.doi.org/10.1253/circj.CJ-21-0901DOI Listing
April 2022

Safety and Efficacy of Burosumab in Pediatric Patients With X-Linked Hypophosphatemia: A Phase 3/4 Open-Label Trial.

J Endocr Soc 2022 May 11;6(5):bvac021. Epub 2022 Feb 11.

Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.

Objective: Burosumab, an anti-fibroblast growth factor 23 antibody, was recently approved for the treatment of X-linked hypophosphatemia (XLH).We evaluated the safety and efficacy of burosumab in pediatric XLH patients.

Methods: This open-label, phase 3/4 trial of ≤ 124 weeks' duration was conducted at 4 Japanese medical centers. Fifteen children aged 1 to 12 years with XLH were included. All had previously been treated with phosphorus or vitamin D. Subcutaneous burosumab was administered every 2 weeks, starting with 0.8 mg/kg, and adjusted based on serum phosphorus levels and any safety concerns (maximum 2 mg/kg). Safety assessments included the frequency of treatment-emergent adverse events (TEAEs). Efficacy of burosumab on biochemical markers, clinical markers of rickets, motor function, and growth was also evaluated.

Results: The average treatment duration was 121.7 weeks. Frequently reported TEAEs were nasopharyngitis (46.7%), dental caries (40.0%), and influenza (33.3%). At baseline, patients had low serum phosphorus concentrations (2.6 ± 0.3 mg/dL) and low-to-normal 1,25-dihydroxyvitamin D concentrations (24.7 ± 12.7 pg/mL), which increased with burosumab treatment and were maintained during the study period. Alkaline phosphatase decreased continuously. At baseline, the mean ± SD total Thacher Rickets Severity Score (RSS) was 1.3 ± 1.2, and 4 patients (26.7%) had an RSS ≥ 2.0. Mean Radiographic Global Impression of Change and RSS tended to improve, particularly in patients with higher baseline RSS. There was a trend toward increased 6-minute walk test distance. No apparent changes in growth rate were observed.

Conclusion: Burosumab has a good safety profile and is effective in pediatric patients with XLH.
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http://dx.doi.org/10.1210/jendso/bvac021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962727PMC
May 2022

Vertebral osteomyelitis caused by the novel pathogen Cutibacterium modestum: a case report.

BMC Infect Dis 2022 Mar 29;22(1):305. Epub 2022 Mar 29.

Department of Infectious Diseases, Japanese Red Cross Ise Hospital, 1-471-2, Funae, Ise, Mie, 516-8512, Japan.

Background: Cutibacterium modestum is one of the five species of the genus Cutibacterium. While C. acnes has been reported as an important pathogen in bone and joint infections, the clinical characteristics of C. modestum infections remain unclear. Moreover, thus far, there has been no clinical case report regarding C. modestum infections.

Case Presentation: An 82-year-old man with a history of repeated trigger point injections for lumbago at the L4 level presented with fever and an exacerbation of lumbago. Physical examination indicated knocking pain at the L4-L5 levels; magnetic resonance imaging showed irregular bone destruction of the L4 vertebral body, and low T1 and high T2 intensity lesions at the L4-L5 intervertebral disc. Two sets of blood cultures (two aerobic and two anaerobic) were performed. Intravenous cefazolin was administered, considering the common pathogens of vertebral osteomyelitis, such as Staphylococcus aureus. The patient's condition did not improve; thereafter, anaerobic culture bottles revealed Gram-positive rods on day 11 of incubation. There was no evidence of infective endocarditis upon transthoracic echocardiography. Needle aspiration from the L4-L5 intervertebral disc was performed on day 13 that also showed the presence of Gram-positive rods. The patient was diagnosed with vertebral osteomyelitis caused by C. modestum using a combination of characteristic peak analysis with matrix-assisted laser desorption ionization (MALDI), microbial biochemistry examinations, and 16S rRNA gene sequencing from the blood and pus cultures. He was successfully treated with alternative intravenous ampicillin, followed by oral amoxicillin for 10 weeks, according to the tests for ampicillin susceptibility, with a minimum inhibitory concentration of 0.016 μg/mL using E-test® under aerobic conditions.

Conclusions: Cutibacterium modestum is a microorganism that is difficult to identify. A combination of characteristic peaks with MALDI, appropriate microbial biochemical examinations, and 16S rRNA gene sequencing may serve as an efficient guide for the identification of C. modestum.
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http://dx.doi.org/10.1186/s12879-022-07290-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962030PMC
March 2022

Insufficiency of hepatocyte growth factor activator inhibitor-1 confers lymphatic invasion of tongue carcinoma cells.

Cancer Sci 2022 Jun 12;113(6):2179-2193. Epub 2022 Apr 12.

Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

Hepatocyte growth factor (HGF) activator inhibitor type-1 (HAI-1), encoded by the SPINT1 gene, is a transmembrane protease inhibitor that regulates membrane-anchored serine proteases, particularly matriptase. Here, we explored the role of HAI-1 in tongue squamous cell carcinoma (TSCC) cells. An immunohistochemical study of HAI-1 in surgically resected TSCC revealed the cell surface immunoreactivity of HAI-1 in the main portion of the tumor. The immunoreactivity decreased in the infiltrative front, and this decrease correlated with enhanced lymphatic invasion as judged by podoplanin immunostaining. In vitro homozygous deletion of SPINT1 (HAI-1KO) in TSCC cell lines (HSC3 and SAS) suppressed the cell growth rate but significantly enhanced invasion in vitro. The loss of HAI-1 resulted in enhanced pericellular activities of proteases, such as matriptase and urokinase-type plasminogen activator, which induced activation of HGF/MET signaling in the co-culture with pro-HGF-expressing fibroblasts and plasminogen-dependent plasmin generation, respectively. The enhanced plasminogen-dependent plasmin generation was abrogated partly by matriptase silencing. Culture supernatants of HAI-1KO cells had enhanced potency for converting the proform of vascular endothelial growth factor-C (VEGF-C), a lymphangiogenesis factor, into the mature form in a plasminogen-dependent manner. Furthermore, HGF significantly stimulated VEGF-C expression in TSCC cells. Orthotopic xenotransplantation into nude mouse tongue revealed enhanced lymphatic invasion of HAI-1KO TSCC cells compared to control cells. Our results suggest that HAI-1 insufficiency leads to dysregulated pericellular protease activity, which eventually orchestrates robust activation of protease-dependent growth factors, such as HGF and VEGF-C, in a tumor microenvironment to contribute to TSCC progression.
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http://dx.doi.org/10.1111/cas.15346DOI Listing
June 2022

Feasibility and safety of coronary catheterization with the distal radial approach for hemodialysis patients.

J Cardiol 2022 08 12;80(2):162-166. Epub 2022 Mar 12.

Department of Cardiovascular Medicine, Kurashiki Central Hospital, Kurashiki, Japan.

Background: The distal radial approach (DRA) has been proposed as an alternative approach for coronary angiography (CAG) and percutaneous coronary intervention (PCI). However, its outcomes in hemodialysis (HD) patients have not been well studied in detail. We aimed to determine the feasibility and safety of coronary intervention with the DRA for HD patients.

Methods: We performed CAG or PCI with the DRA in 2500 consecutive patients between October 2018 and February 2020. The patients included 98 HD patients (HD group) and 2402 non-HD patients (non-HD group). The primary endpoints were the rates of procedural success and puncture site-related complications. The secondary endpoints were puncture site-related complications one year after the procedure. As a subanalysis, we also compared the outcomes on the basis of CAG and PCI.

Results: The procedural success rates were similar in the HD and non-HD groups (80.6% vs. 82.6%, p = 0.61 for the entire cohort; 78.3% vs. 80.9%, p = 0.58 for CAG; and 86.2% vs. 88.0%, p = 0.78 for PCI). The bleeding complications rates were low and there was no difference between groups (6.1% vs. 4.1%, p = 0.33 for the entire cohort; 0% vs. 2.2%, p = 0.21 for CAG; and 20.7% vs. 10.3%, p = 0.079 for PCI). Radial artery occlusion occurred in only one patient in the HD group after the procedure.

Conclusions: Although modified hemostasis methods could be necessary for HD patients undergoing PCI, coronary intervention with the DRA is feasible and safe for both HD and non-HD patients.
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http://dx.doi.org/10.1016/j.jjcc.2022.02.014DOI Listing
August 2022

Comparison of original and modified Academic Research Consortium for High Bleeding Risk definitions in real-world practice.

J Cardiol 2022 08 10;80(2):155-161. Epub 2022 Mar 10.

Department of Cardiology, Kurashiki Central Hospital, Kurashiki, Japan. Electronic address:

Background: The Academic Research Consortium for High Bleeding Risk (ARC-HBR) defined high bleeding risk (HBR) in patients undergoing percutaneous coronary intervention. We have reported a simplified HBR (S-HBR), excluding six items with prevalences under 1% from ARC-HBR. The Japanese Circulation Society developed an HBR specific to Japanese (J-HBR), adding three items to ARC-HBR in consideration of ethnicity. Data comparing each HBR are scarce.

Methods: Patients treated with second-generation drug-eluting stents between January 2010 and December 2013 were enrolled, in whom all items of ARC-HBR, and the incidences of major bleeding and ischemic events were examined. Also, the diagnostic values of ARC-HBR, S-HBR, and J-HBR at 1 and 7 years post procedure were compared by using receiver-operating characteristic curves.

Results: The study sample consisted of 3430 patients. Mean follow-up period was 2299 ± 904 days. The incidence of major bleeding at 1 and 7 years in each definition was as follows: ARC-HBC, 3.3% and 10.6%; S-HBR, 3.3% and 10.7%; and J-HBR, 2.9% and 10.0%. The diagnostic value of J-HBR for major bleeding at 1 year was lower than that of ARC-HBR (C statistics 0.64 vs. 0.68, p < 0.001). Other diagnostic values of S-HBR and J-HBR were comparable to those of ARC-HBR.

Conclusions: S-HBR was as useful as ARC-HBR in predicting both short- and long-term HBR, and J-HBR is useful for predicting long-term HBR.
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http://dx.doi.org/10.1016/j.jjcc.2022.02.018DOI Listing
August 2022

Data-Driven Optimization and Experimental Validation for the Lab-Scale Mono-Like Silicon Ingot Growth by Directional Solidification.

ACS Omega 2022 Mar 17;7(8):6665-6673. Epub 2022 Feb 17.

Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.

The casting mono-like silicon (Si) grown by directional solidification (DS) is promising for high-efficiency solar cells. However, high dislocation clusters around the top region are still the practical drawbacks, which limit its competitiveness to the monocrystalline Si. To optimize the DS-Si process, we applied the framework, which integrates the growing experiments, transient global simulations, artificial neuron network (ANN) training, and genetic algorithms (GAs). First, we grew the Si ingot by the original recipe and reproduced it with transient global modeling. Second, predictions of the Si ingot domain from different recipes were used to train the ANN, which acts as the instant predictor of ingot properties from specific recipes. Finally, the GA equipped with the predictor searched for the optimal recipe according to multi-objective combination, such as the lowest residual stress and dislocation density. We also implemented the optimal recipe in our mono-like DS-Si process for verification and comparison. According to the optimal recipe, we could reduce the dislocation density and smooth the growth rate during the Si ingot growing process. Comparisons of the growth interface and grain boundary evolutions showed the decrease of the interface concavity and the multi-crystallization in the top part of the ingot. The well-trained ANN combined with the GA could derive the optimal growth parameter combinations instantly and quantitatively for the multi-objective processes.
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http://dx.doi.org/10.1021/acsomega.1c06018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892659PMC
March 2022

Myeloid cell thrombus and fetal vascular malperfusion in placentas with transient abnormal myelopoiesis.

Virchows Arch 2022 Jun 24;480(6):1181-1187. Epub 2022 Feb 24.

Department of Diagnostic Pathology, Faculty of Medicine, Miyazaki University Hospital, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.

Transient abnormal myelopoiesis (TAM), also known as transient myeloproliferative disorder or transient leukemia, is a self-regressing neoplasia that afflicts infants with trisomy 21. A recent review article documented "myeloid cell thrombus (MCT)" and "fetal vascular malperfusion (FVM)" in placentas with TAM, although the characteristic TAM placental findings have not been clarified. Here, we compared the clinical and pathological placental findings between trisomy 21 patients with or without TAM. In 13 cases of trisomy 21, we identified six placentas with TAM and seven placentas without TAM. The six placentas with TAM included two stillborn cases. Microscopically, MCT was noted in all the cases, and a high incidence of FVM (50%) was observed in TAM cases. Immunohistochemically, MCT was found to be a platelet-rich thrombus. The placentas were grouped according to the presence or absence of TAM and subsequently compared. Clinically, the incidences of abnormal fetal heart rate pattern and fetal or neonatal death were significantly higher in TAM cases. Pathologically, placenta in TAM cases weighted more than those in cases without TAM, and the incidence of MCT was significantly higher in placentas with TAM. Moreover, the incidence of FVM was higher in placentas with TAM, but this difference was not statistically significant. We propose that MCT is a diagnostic feature of placentas with TAM and may be associated with poor fetal outcomes.
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http://dx.doi.org/10.1007/s00428-022-03289-5DOI Listing
June 2022

Lateral flow immunoassay for small-molecules detection in phytoproducts: a review.

J Nat Med 2022 Jun 16;76(3):521-545. Epub 2022 Feb 16.

Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Phytoproducts are involved in various fields of industry. Small-molecule (Mw < 900 Da) organic compounds can be used to indicate the quality of plant samples in the perspective of efficacy by measuring the necessary secondary metabolites and in the perspective of safety by measuring the adulterant level of toxic compounds. The development of reliable detection methods for these compounds in such a complicated matrix is challenging. The lateral flow immunoassay (LFA) is one of the immunoassays well-known for its simplicity, portability, and rapidity. In this review, the general principle, components, format, and application of the LFA for phytoproducts are discussed.
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http://dx.doi.org/10.1007/s11418-022-01605-6DOI Listing
June 2022

Transabdominal ultrasonographic diagnosis of relatively rare pancreatic neoplasms.

J Med Ultrason (2001) 2022 Apr 12;49(2):187-197. Epub 2022 Feb 12.

Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, 1‑98 Dengakugakubo, Kutukake‑cho, Toyoake, Aichi, 470‑1192, Japan.

There are various types of pancreatic neoplasms, and their prognosis and treatment methods are different. Therefore, accurate diagnosis is important to determine the best treatment strategy. Transabdominal ultrasonography is frequently used as a screening examination for diagnostic imaging of pancreatic neoplasms. In this review, we have focused on the characteristics of ultrasonic findings for relatively rare pancreatic neoplasms.
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http://dx.doi.org/10.1007/s10396-022-01192-9DOI Listing
April 2022

Harringtonine Ester Derivatives with Enhanced Antiproliferative Activities against HL-60 and HeLa Cells.

J Nat Prod 2022 02 11;85(2):345-351. Epub 2022 Feb 11.

Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Harringtonine (HT), produced from species, is known to exhibit potent antiproliferative activity against myeloid leukemia cells by inhibiting protein synthesis. A previous study using acute promyelocytic leukemia (HL-60) cells raised the possibility that the C-5' methyl group of HT plays an important role in regulating leukemia cell line antiproliferative activity. In order to investigate the effect of hydrocarbon chains at C-5' on the resultant activity, the C-5' methyl group was replaced with various straight- and branched-chain hydrocarbons using the corresponding alcohols, and their antiproliferative activity against HL-60 and HeLa cells was investigated. As a result, 4'--heptyl-4'-demethylharringtonine (, -heptyl derivative) showed the most potent cytotoxicity among the HT ester derivatives produced, with IC values of 9.4 nM and 0.4 μM for HL-60 and HeLa cells, respectively. Interestingly, the cytotoxicity of derivative against HL-60 and HeLa cells respectively was ∼5 (IC = 50.5 nM) and ∼10 times (IC = 4.0 μM) those of HT and ∼2 (IC = 21.8 nM) and ∼4 times (IC = 1.7 μM) more than homoharringtonine (HHT). These results demonstrate the potential of the derivative as a lead compound against leukemia.
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http://dx.doi.org/10.1021/acs.jnatprod.1c00888DOI Listing
February 2022

Mid-term results of mitral valve reconstruction with autologous pericardial patch for active infective endocarditis with extensive leaflet destruction.

Gen Thorac Cardiovasc Surg 2022 Feb 9. Epub 2022 Feb 9.

Department of Cardiovascular Surgery, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan.

Objectives: This study aimed to evaluate the outcomes of our repair technique using autologous pericardial patches for active infective endocarditis with extensive mitral valve destruction.

Methods: From 2009 through 2016, 12 patients with extensive mitral leaflet destruction due to infective endocarditis underwent mitral valve repair with an autologous pericardial patch. Mid-term clinical outcomes and echocardiographic findings of these patients were retrospectively assessed.

Results: The perioperative mortality rate was 8.3% (1/12). Postoperatively, the mitral regurgitation grade was ≤ 1 + in all patients. During 5.0 ± 3.2 years of follow-up, there was no recurrence of infective endocarditis or death. There were no cases of mitral regurgitation grade >  + 1 and pressure gradient > 5 mmHg during follow-up among 6 patients who underwent posterior leaflet reconstruction, whereas elevation of the pressure gradient was observed in patients who underwent reconstruction of two areas of the anterior leaflet and survived up till the follow-up phase among 3 patients who underwent anterior leaflet repair. The mitral regurgitation grade worsened and pressure gradient was elevated during the follow-up phase in the 2 patients who underwent bi-leaflet repair, and reoperation was performed.

Conclusion: Mitral valve reconstruction using autologous pericardial patch is a useful treatment option for extensive mitral valve destruction due to active infective endocarditis. Our clinical data revealed that good mid-term results were obtained for posterior leaflet lesions, while extensive anterior leaflet and bi-leaflet lesion repair did not yield satisfactory results. The indication for surgical repair should be carefully evaluated when an extensive anterior region is involved.
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http://dx.doi.org/10.1007/s11748-022-01776-9DOI Listing
February 2022

-infected aneurysm and vertebral osteomyelitis in an immunocompetent patient.

IDCases 2022 27;27:e01426. Epub 2022 Jan 27.

Department of Infectious Diseases, Japanese Red Cross Ise Hospital, Ise 516-8512, Japan.

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http://dx.doi.org/10.1016/j.idcr.2022.e01426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8808053PMC
January 2022
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