115 results on '"Igari H"'
Search Results
2. Comparative utility of interferon-γ release assay, QuantiFERON® TB-GIT and T-SPOT®.TB in rheumatoid arthritis
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Matsumura, R., primary, Igari, H., additional, Nakazawa, T., additional, Ishikawa, S., additional, Tsuyuzaki, M., additional, Suzuki, K., additional, and Yamagishi, F., additional
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- 2016
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3. Risk of developing active tuberculosis in rheumatoid arthritis patients on adalimumab in Japan
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Watanabe, A., primary, Matsumoto, T., additional, Igari, H., additional, Sawa, J., additional, Yamaguchi, Y., additional, and Sakatani, M., additional
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- 2016
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4. Comparison of specificities between two interferon-gamma release assays in Japan [Short communication]
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Higuchi, K., primary, Sekiya, Y., additional, Igari, H., additional, Watanabe, A., additional, and Harada, N., additional
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- 2012
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5. Effects of water flow volume on the isolation of bacteria from motion sensor faucets
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Nakamura, Y., primary, Watanabe, M., additional, Kubo, E., additional, Suzuki, A., additional, Igari, H., additional, Kitada, M., additional, and Sato, T., additional
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- 2011
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6. Robust Wireless Sensor Network Featuring Automatic Function Alternation.
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Miyazaki, T., Shitara, D., Kawano, R., Endo, Y., Tanno, Y., and Igari, H.
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- 2011
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7. A Function Alternation Algorithm for Wireless Sensor Networks.
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Shitara, D., Miyazaki, T., and Igari, H.
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- 2010
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8. 828 Preliminary trial of lung cancer screening using mobile CT
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Nagao, K., primary, Uruma, T., additional, Shimura, A., additional, Igari, H., additional, Yabe, T., additional, Matsumoto, T., additional, Yamagishi, F., additional, Takiguchi, Y., additional, and Kuriyama, T., additional
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- 1997
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9. Pregnancy-Associated Glycoprotein (PAG) in Patients with Cancers : Synthesis from Leukocytes and Presence in the Pathologic Mucous Membrane of Colon
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Kasukawa, R., Onami, K., Ohara, M., Igari, H., and Yoshida, H.
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- 1983
10. The value of plain radiographs in the prediction of outcome in pelvic fractures treated with embolisation therapy.
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Niwa, T, Takebayashi, S, Igari, H, Morimura, N, Uchida, K, Sugiyama, M, and Matsubara, S
- Abstract
40 haemodynamically unstable patients with pelvic injuries were studied to assess the ability of plain radiographs to detect haemorrhagic sites. Pelvic radiographs and bilateral angiograms were reviewed separately for detection of haemorrhagic sites in both anterior and posterior segments. Sensitivity and specificity of pelvic radiographs for the detection of haemorrhagic sites were obtained by analysis of angiographic findings. Angiography demonstrated arterial injury in 106 divisions: 26 right anterior, 22 right posterior, 33 left anterior and 25 left posterior. Sensitivities of the radiographs for predicting haemorrhagic sites were higher in the anterior segment (right, 96%; left, 100%) than in the posterior segment (right, 73%; left, 83%). However, specificities were lower in the anterior segment (right, 79%; left, 78%) than in the posterior segment (right, 100%; left, 100%). In 15 (58%) of 26 patients with in-dwelling Foley catheters, including those with catheter deviation, the severity of anterior injury indicated on plain radiographs was correlated with angiographic findings. Plain radiographs of the pelvis proved useful for predicting haemorrhagic sites in haemodynamically unstable patients with pelvic fractures, especially in those with anterior fractures.
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- 2000
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11. Role of carotid body in pressure response of pulmonary circulation in rats
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Sugito, K., Tatsumi, K., Igari, H., Kasahara, Y., Tani, T., Kimura, H., Hayashi, F., and Kuriyama, T.
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- 1998
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12. Clinical study of ischemic colitis - An attempt at clinical classification by prospective and retrospective analysis of radiographic findings.
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Kurihara, Y., primary, Suzuki, S., additional, Wada, T., additional, Igari, H., additional, Obara, K., additional, Igarashi, T., additional, Kasukawa, R., additional, Sato, H., additional, Oohara, M., additional, Kodama, T., additional, Tanji, N., additional, Sato, K., additional, Fukuhara, K., additional, and Kawarada, Y., additional
- Published
- 1985
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13. Two cases of inversion of the appendiceal stump.
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Ishibashi, K., primary, Yokogi, K., additional, Igari, H., additional, Kurihara, Y., additional, and Kasukawa, R., additional
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- 1989
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14. Intractable ischemic colitis in the sigmoid colon - A case report.
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Kurihara, Y., primary, Suzuki, S., additional, Wada, T., additional, Igari, H., additional, Obara, K., additional, Igarashi, T., additional, Kasukawa, R., additional, Tsuchiya, A., additional, Watanabe, I., additional, and Endoh, S., additional
- Published
- 1986
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15. Factors Associated with Defecation Satisfaction among Japanese Adults with Chronic Constipation.
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Yamamoto S, Ohashi W, Yamaguchi Y, Igari H, Koshino A, Sugiyama T, Nagao K, Tamura Y, Izawa S, Mano M, Ebi M, Usami J, Hamano K, Izumi J, Wakita Y, Funaki Y, Ogasawara N, Sasanabe R, Sasaki M, Maekawa M, and Kasugai K
- Abstract
Background: Constipation causes substantial morbidity worldwide. Methods: This survey assessed constipation-related factors in Japan using the Japanese version of the Irritable Bowel Syndrome Quality of Life (IBS-QOL-J) instrument. We also examined the relationship among laxative type, Bristol Stool Form Scale (BSFS) scores, and treatment cost. Finally, we examined differences in satisfaction scores according to laxative type, treatment type, treatment cost, and BSFS score. Results: IBS-QOL-J was higher among those taking salt and/or irritation laxatives. Those paying >JPY 5000 (USD 50.00) had the lowest IBS-QOL-J. IBS-QOL-J was significantly lower among those with a BSFS score of 1 or 2 (severe constipation). Conclusions: This study's findings suggest that a variety of factors, including treatment type and cost, are associated with defecation satisfaction. Those who had hard stools, used multiple laxatives, or spent more on treatment were less satisfied. Future strategies should target therapies that do not require multiple laxatives with lower treatment costs. Adequate defecation with a small number of appropriate laxatives at minimal cost appears to improve defecation satisfaction. It is desirable to identify appropriate laxatives and improve dietary habits and exercise routines. It is also necessary to stop blindly increasing laxative usage and properly diagnose constipation disorders such as anatomical abnormalities other than functional constipation.
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- 2024
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16. Dynamic diversity of SARS-CoV-2 genetic mutations in a lung transplantation patient with persistent COVID-19.
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Igari H, Sakao S, Ishige T, Saito K, Murata S, Yahaba M, Taniguchi T, Suganami A, Matsushita K, Tamura Y, Suzuki T, and Ido E
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- Humans, Male, Antiviral Agents therapeutic use, Immunocompromised Host, Adenosine Monophosphate therapeutic use, Drug Resistance, Viral genetics, Middle Aged, COVID-19 Drug Treatment, Lung Diseases, Interstitial genetics, Lung Diseases, Interstitial virology, SARS-CoV-2 genetics, COVID-19 virology, Lung Transplantation, Mutation, Alanine analogs & derivatives, Alanine therapeutic use, Adenosine Monophosphate analogs & derivatives, Coronavirus RNA-Dependent RNA Polymerase
- Abstract
Numerous SARS-CoV-2 variant strains with altered characteristics have emerged since the onset of the COVID-19 pandemic. Remdesivir (RDV), a ribonucleotide analogue inhibitor of viral RNA polymerase, has become a valuable therapeutic agent. However, immunosuppressed hosts may respond inadequately to RDV and develop chronic persistent infections. A patient with respiratory failure caused by interstitial pneumonia, who had undergone transplantation of the left lung, developed COVID-19 caused by Omicron BA.5 strain with persistent chronic viral shedding, showing viral fusogenicity. Genome-wide sequencing analyses revealed the occurrence of several viral mutations after RDV treatment, followed by dynamic changes in the viral populations. The C799F mutation in nsp12 was found to play a pivotal role in conferring RDV resistance, preventing RDV-triphosphate from entering the active site of RNA-dependent RNA polymerase. The occurrence of diverse mutations is a characteristic of SARS-CoV-2, which mutates frequently. Herein, we describe the clinical case of an immunosuppressed host in whom inadequate treatment resulted in highly diverse SARS-CoV-2 mutations that threatened the patient's health due to the development of drug-resistant variants., (© 2024. The Author(s).)
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- 2024
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17. Suppression of Type I Interferon Signaling in Myeloid Cells by Autoantibodies in Severe COVID-19 Patients.
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Aoki A, Iwamura C, Kiuchi M, Tsuji K, Sasaki A, Hishiya T, Hirasawa R, Kokubo K, Kuriyama S, Onodera A, Shimada T, Nagaoka T, Ishikawa S, Kojima A, Mito H, Hase R, Kasahara Y, Kuriyama N, Nakamura S, Urushibara T, Kaneda S, Sakao S, Nishida O, Takahashi K, Kimura MY, Motohashi S, Igari H, Ikehara Y, Nakajima H, Suzuki T, Hanaoka H, Nakada TA, Kikuchi T, Nakayama T, Yokote K, and Hirahara K
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- Female, Humans, Male, Dendritic Cells immunology, SARS-CoV-2 immunology, Severity of Illness Index, Signal Transduction immunology, Autoantibodies immunology, Autoantibodies blood, COVID-19 immunology, Interferon Type I immunology, Interferon Type I metabolism, Myeloid Cells immunology
- Abstract
Purpose: Auto-antibodies (auto-abs) to type I interferons (IFNs) have been identified in patients with life-threatening coronavirus disease 2019 (COVID-19), suggesting that the presence of auto-abs may be a risk factor for disease severity. We therefore investigated the mechanism underlying COVID-19 exacerbation induced by auto-abs to type I IFNs., Methods: We evaluated plasma from 123 patients with COVID-19 to measure auto-abs to type I IFNs. We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from the patients with auto-abs and conducted epitope mapping of the auto-abs., Results: Three of 19 severe and 4 of 42 critical COVID-19 patients had neutralizing auto-abs to type I IFNs. Patients with auto-abs to type I IFNs showed no characteristic clinical features. scRNA-seq from 38 patients with COVID-19 revealed that IFN signaling in conventional dendritic cells and canonical monocytes was attenuated, and SARS-CoV-2-specific BCR repertoires were decreased in patients with auto-abs. Furthermore, auto-abs to IFN-α2 from COVID-19 patients with auto-abs recognized characteristic epitopes of IFN-α2, which binds to the receptor., Conclusion: Auto-abs to type I IFN found in COVID-19 patients inhibited IFN signaling in dendritic cells and monocytes by blocking the binding of type I IFN to its receptor. The failure to properly induce production of an antibody to SARS-CoV-2 may be a causative factor of COVID-19 severity., (© 2024. The Author(s).)
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- 2024
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18. Fungemia With Wickerhamomyces anomalus: A Case Report and Literature Review.
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Sakai Y, Taniguchi T, Herai Y, Yahaba M, Watanabe A, Kamei K, and Igari H
- Abstract
We report the case of an 84-year-old man with a history of IgG4-related sclerosing cholangitis who was diagnosed with advanced esophageal cancer and underwent radiation and chemotherapy. An implantable central venous access port was placed for chemotherapy and total parenteral nutrition. The patient presented with a fever and received antimicrobial therapy for acute cholangitis but remained febrile, and subsequently, yeast was detected in the aerobic bottle of blood culture obtained from the central venous line. The yeast was identified as Wickerhamomyces anomalus . Liposomal amphotericin B was administered, and the central line access port was removed. After confirmation of negative blood cultures and 14 days post treatment, he underwent reinsertion of the central line access port. Due to persistent pain at the insertion site, fluconazole was added for an additional 14 days, and the patient was discharged and transferred to another hospital. Wickerhamomyces anomalus is a rare fungal infection with other synonyms including Pichia anomala , Hansenula anomala , and Candida pelliculosa . A literature review of 53 case reports of Wickerhamomyces anomalus , Pichia anomala , Hansenula anomala , and Candida pelliculosa was conducted, with a total of 211 cases reviewed. Fungemia was reported in 94% of cases, with central venous catheterization, parental feeding, low birth weight, and immunocompromised status identified as major risk factors. The majority of cases were pediatric, particularly neonatal, and there were reports of nosocomial infections causing outbreaks, with some cases involving the eye such as endophthalmitis or keratitis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Sakai et al.)
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- 2024
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19. Infectious virus shedding duration reflects secretory IgA antibody response latency after SARS-CoV-2 infection.
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Miyamoto S, Nishiyama T, Ueno A, Park H, Kanno T, Nakamura N, Ozono S, Aihara K, Takahashi K, Tsuchihashi Y, Ishikane M, Arashiro T, Saito S, Ainai A, Hirata Y, Iida S, Katano H, Tobiume M, Tokunaga K, Fujimoto T, Suzuki M, Nagashima M, Nakagawa H, Narita M, Kato Y, Igari H, Fujita K, Kato T, Hiyama K, Shindou K, Adachi T, Fukushima K, Nakamura-Uchiyama F, Hase R, Yoshimura Y, Yamato M, Nozaki Y, Ohmagari N, Suzuki M, Saito T, Iwami S, and Suzuki T
- Subjects
- Humans, SARS-CoV-2, Virus Shedding, Antibody Formation, Reaction Time, Antibodies, Viral, RNA, Viral, Immunoglobulin G, Immunoglobulin A, Immunoglobulin A, Secretory, COVID-19
- Abstract
Infectious virus shedding from individuals infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is used to estimate human-to-human transmission risk. Control of SARS-CoV-2 transmission requires identifying the immune correlates that protect infectious virus shedding. Mucosal immunity prevents infection by SARS-CoV-2, which replicates in the respiratory epithelium and spreads rapidly to other hosts. However, whether mucosal immunity prevents the shedding of the infectious virus in SARS-CoV-2-infected individuals is unknown. We examined the relationship between viral RNA shedding dynamics, duration of infectious virus shedding, and mucosal antibody responses during SARS-CoV-2 infection. Anti-spike secretory IgA antibodies (S-IgA) reduced viral RNA load and infectivity more than anti-spike IgG/IgA antibodies in infected nasopharyngeal samples. Compared with the IgG/IgA response, the anti-spike S-IgA post-infection responses affected the viral RNA shedding dynamics and predicted the duration of infectious virus shedding regardless of the immune history. These findings highlight the importance of anti-spike S-IgA responses in individuals infected with SARS-CoV-2 for preventing infectious virus shedding and SARS-CoV-2 transmission. Developing medical countermeasures to shorten S-IgA response time may help control human-to-human transmission of SARS-CoV-2 infection and prevent future respiratory virus pandemics., Competing Interests: Competing interests statement:The authors declare no competing interest.
- Published
- 2023
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20. Virological outcomes of various first-line ART regimens in patients harbouring HIV-1 E157Q integrase polymorphism: a multicentre retrospective study.
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Uno S, Gatanaga H, Hayashida T, Imahashi M, Minami R, Koga M, Samukawa S, Watanabe D, Fujii T, Tateyama M, Nakamura H, Matsushita S, Yoshino Y, Endo T, Horiba M, Taniguchi T, Moro H, Igari H, Yoshida S, Teshima T, Nakajima H, Nishizawa M, Yokomaku Y, Iwatani Y, Hachiya A, Kato S, Hasegawa N, Yoshimura K, Sugiura W, and Kikuchi T
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- Humans, Retrospective Studies, Raltegravir Potassium therapeutic use, Heterocyclic Compounds, 3-Ring therapeutic use, Drug Resistance, Viral genetics, HIV-1 genetics, HIV Infections drug therapy, HIV Integrase Inhibitors therapeutic use, HIV Integrase Inhibitors pharmacology, HIV Integrase genetics
- Abstract
Background: Integrase strand transfer inhibitors (INSTIs) are recommended as first-line ART for people living with HIV (PLWH) in most guidelines. The INSTI-resistance-associated mutation E157Q, a highly prevalent (2%-5%) polymorphism of the HIV-1 (human immunodeficiency virus type 1) integrase gene, has limited data on optimal first-line ART regimens. We assessed the virological outcomes of various first-line ART regimens in PLWH with E157Q in real-world settings., Methods: A multicentre retrospective observational study was conducted on PLWH who underwent integrase genotypic drug-resistance testing before ART initiation between 2008 and 2019 and were found to have E157Q. Viral suppression (<50 copies/mL) rate at 24 and 48 weeks, time to viral suppression and time to viral rebound (≥100 copies/mL) were compared among the first-line ART regimens., Results: E157Q was detected in 167 (4.1%) of 4043 ART-naïve PLWH. Among them, 144 had available clinical data after ART initiation with a median follow-up of 1888 days. Forty-five started protease inhibitors + 2 NRTIs (PI group), 33 started first-generation INSTI (raltegravir or elvitegravir/cobicistat) + 2 NRTIs (INSTI-1 group), 58 started once-daily second-generation INSTI (dolutegravir or bictegravir) + 2 NRTIs (INSTI-2 group) and eight started other regimens. In the multivariate analysis, the INSTI-2 group showed similar or favourable outcomes compared with the PI group for viral suppression rates, time to viral suppression and time to viral rebound. Two cases in the INSTI-1 group experienced virological failure., Conclusions: The general guideline recommendation of second-generation INSTI-based first-line ART for most PLWH is also applicable to PLWH harbouring E157Q., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
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21. Factors Influencing the Indeterminate Results in a T-SPOT.TB test: A Matched Case-control Study.
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Herai Y, Yahaba M, Taniguchi T, Murata S, Chiba H, and Igari H
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- Humans, Case-Control Studies, Retrospective Studies, Interferon-gamma, Tuberculin Test, Interferon-gamma Release Tests, Mitogens, Human T-lymphotropic virus 1
- Abstract
Objective A T-SPOT.TB can yield indeterminate results under two test observation conditions: a high response to the nil in negative control wells (high nil-control) or a low response to the mitogen in positive control wells (low mitogen-control). The most strongly influential factors for these indeterminate results, however, have yet to be identified. Methods From June 1, 2015, to June 30, 2021, we conducted a 1:1 matched case-control, retrospective study. Patients Patients who underwent a T-SPOT.TB test at Chiba University Hospital. Results The study included 5,956 participants. Indeterminate results were found in 63 participants (1.1%), including high nil-control in 37 and low mitogen-control in 26. Human T-cell leukemia virus type 1 (HTLV-1) positivity was the only influencing factor associated with high nil-control (adjusted odds ratio=98.5, 95% confidence interval: 6.59-1,480). Conclusion Regarding the indeterminate results, all HTLV-1 positive participants had a high nil response and no low mitogen response. It was suspected that abnormally produced interferon γ caused a nonspecific reaction to the negative control well, resulting in a high nil response. Low mitogen-control, conversely, did not appear to have any statistically significant influential factors.
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- 2023
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22. A Comparison of Clinical Presentations in Coronavirus Disease 2019 Caused by Different Omicron Variants in Japan: A Retrospective Study.
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Hirama R, Takeda K, Sakao S, Kasai H, Miyata S, Shikano K, Naito A, Abe M, Kawasaki T, Shigeta A, Nakada TA, Igari H, and Suzuki T
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- Humans, Retrospective Studies, Japan epidemiology, SARS-CoV-2, COVID-19 epidemiology, Cross Infection
- Abstract
Objective We evaluated the clinical differences in coronavirus disease 2019 (COVID-19) patients between the sixth wave with the Omicron BA.1/BA.2 dominant variant (from January to April 2022) and seventh wave with the Omicron BA.5 dominant variant (from July to August 2022). Methods This retrospective, single-center, observational study included COVID-19 patients admitted to our institution in the sixth wave (sixth-wave group) and the seventh wave (seventh-wave group). Inter-group comparisons of clinical presentations, the prognosis, and proportion of nosocomial infections were performed. Results A total of 190 patients were included (93 and 97 patients in the sixth- and seventh-wave groups, respectively). While there were no significant differences in severity, significantly more patients developed pneumonia caused by COVID-19 in the sixth-wave group than in the seventh-wave group. Although there was no marked difference in in-hospital deaths, more patients died from COVID-19 in the sixth-wave group than in the seventh-wave group. There were significantly more COVID-19 inpatients with nosocomial infections in the seventh-wave group than in the sixth-wave group. Pneumonia from COVID-19 was significantly more severe in the sixth-wave group than in the seventh-wave group. Conclusion COVID-19 patients in the seventh wave are at a lower risk of pneumonia than those in the sixth wave. However, even in the seventh wave, patients with underlying diseases have a risk of death because of the exacerbation of underlying diseases triggered by COVID-19.
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- 2023
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23. Association of demographics, HCV co-infection, HIV-1 subtypes and genetic clustering with late HIV diagnosis: a retrospective analysis from the Japanese Drug Resistance HIV-1 Surveillance Network.
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Otani M, Shiino T, Hachiya A, Gatanaga H, Watanabe D, Minami R, Nishizawa M, Teshima T, Yoshida S, Ito T, Hayashida T, Koga M, Nagashima M, Sadamasu K, Kondo M, Kato S, Uno S, Taniguchi T, Igari H, Samukawa S, Nakajima H, Yoshino Y, Horiba M, Moro H, Watanabe T, Imahashi M, Yokomaku Y, Mori H, Fujii T, Takada K, Nakamura A, Nakamura H, Tateyama M, Matsushita S, Yoshimura K, Sugiura W, Matano T, and Kikuchi T
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- Male, Humans, Hepacivirus, Homosexuality, Male, East Asian People, Phylogeny, Retrospective Studies, Cluster Analysis, Demography, HIV-1, Sexual and Gender Minorities, HIV Infections, Hepatitis C
- Abstract
Introduction: Late diagnosis of the human immunodeficiency virus (HIV) is a major concern epidemiologically, socially and for national healthcare systems. Although the association of certain demographics with late HIV diagnosis has been reported in several studies, the association of other factors, including clinical and phylogenetic factors, remains unclear. In the present study, we conducted a nationwide analysis to explore the association of demographics, clinical factors, HIV-1 subtypes/circulating recombinant form (CRFs) and genetic clustering with late HIV diagnosis in Japan, where new infections mainly occur among young men who have sex with men (MSM) in urban areas., Methods: Anonymized data on demographics, clinical factors and HIV genetic sequences from 39.8% of people newly diagnosed with HIV in Japan were collected by the Japanese Drug Resistance HIV-1 Surveillance Network from 2003 to 2019. Factors associated with late HIV diagnosis (defined as HIV diagnosis with a CD4 count <350 cells/μl) were identified using logistic regression. Clusters were identified by HIV-TRACE with a genetic distance threshold of 1.5%., Results: Of the 9422 people newly diagnosed with HIV enrolled in the surveillance network between 2003 and 2019, 7752 individuals with available CD4 count at diagnosis were included. Late HIV diagnosis was observed in 5522 (71.2%) participants. The overall median CD4 count at diagnosis was 221 (IQR: 62-373) cells/μl. Variables independently associated with late HIV diagnosis included age (adjusted odds ratio [aOR] 2.21, 95% CI 1.88-2.59, ≥45 vs. ≤29 years), heterosexual transmission (aOR 1.34, 95% CI 1.11-1.62, vs. MSM), living outside of Tokyo (aOR 1.18, 95% CI 1.05-1.32), hepatitis C virus (HCV) co-infection (aOR 1.42, 95% CI 1.01-1.98) and not belonging to a cluster (aOR 1.30, 95% CI 1.12-1.51). CRF07_BC (aOR 0.34, 95% CI 0.18-0.65, vs. subtype B) was negatively associated with late HIV diagnosis., Conclusions: In addition to demographic factors, HCV co-infection, HIV-1 subtypes/CRFs and not belonging to a cluster were independently associated with late HIV diagnosis in Japan. These results imply the need for public health programmes aimed at the general population, including but not limited to key populations, to encourage HIV testing., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)
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- 2023
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24. [Neuropathic Pain].
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Igari H and Ushida T
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- Animals, Rabbits, Analgesics, Analgesics, Opioid, Selective Serotonin Reuptake Inhibitors, Neuralgia, Tramadol therapeutic use
- Abstract
Many diseases are associated with "neuropathic pain", which is not usually manageable with common analgesics, such as NSAIDs and acetaminophen. Calcium ion channel α2δ ligands, serotonin-noradrenaline reuptake inhibitors, and tricyclic antidepressants have been used as first-line drugs. If there are no improvements after using these drugs for a while, vaccinia virus inoculation of rabbit inflammatory skin extract, tramadol, and eventually opioid analgesics, may be considered.
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- 2023
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25. Multicenter, single-blind, randomized controlled study of the efficacy and safety of favipiravir and nafamostat mesilate in patients with COVID-19 pneumonia.
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Ikeda M, Okugawa S, Kashiwabara K, Moritoyo T, Kanno Y, Jubishi D, Hashimoto H, Okamoto K, Tsushima K, Uchida Y, Mitsumura T, Igari H, Tsutsumi T, Araoka H, Yatera K, Yamamoto Y, Nakamura Y, Otani A, Yamashita M, Wakimoto Y, Shinohara T, Adachi-Katayama M, Oyabu T, Kanematsu A, Harada S, Takeshita Y, Nakano Y, Miyazaki Y, Sakao S, Saito M, Ogura S, Yamasaki K, Kawasuji H, Hataji O, Inoue JI, Seto Y, and Moriya K
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- Humans, SARS-CoV-2, Antiviral Agents therapeutic use, Single-Blind Method, Disease Progression, Treatment Outcome, COVID-19
- Abstract
Objectives: To evaluate the efficacy and safety of nafamostat combined with favipiravir for the treatment of COVID-19., Methods: We conducted a multicenter, randomized, single-blind, placebo-controlled, parallel assignment study in hospitalized patients with mild-to-moderate COVID-19 pneumonia. Patients were randomly assigned to receive favipiravir alone (n = 24) or nafamostat with favipiravir (n = 21). The outcomes included changes in the World Health Organization clinical progression scale score, time to improvement in body temperature, and improvement in oxygen saturation (SpO
2 )., Results: There was no significant difference in the changes in the clinical progression scale between nafamostat with favipiravir and favipiravir alone groups (median, -0.444 vs -0.150, respectively; least-squares mean difference, -0.294; P = 0.364). The time to improvement in body temperature was significantly shorter in the combination group (5.0 days; 95% confidence interval, 4.0-7.0) than in the favipiravir group (9.0 days; 95% confidence interval, 7.0-18.0; P =0.009). The changes in SpO2 were greater in the combination group than in the favipiravir group (0.526% vs -1.304%, respectively; least-squares mean difference, 1.831; P = 0.022). No serious adverse events or deaths were reported, but phlebitis occurred in 57.1% of the patients in the combination group., Conclusion: Although our study showed no differences in clinical progression, earlier defervescence, and recovery of SpO2 were observed in the combination group., Competing Interests: Declaration of competing interest JI, YS, and KM are co-inventors on patent applications of nafamostat as an antiviral agent (PCT/JP2021/9968, patent applicant: the University of Tokyo). All other authors declare no competing interests. FUJIFILM Toyama Chemical and Nichi-Iko supplied the favipiravir and nafamostat mesilate, respectively., (Copyright © 2022. Published by Elsevier Ltd.)- Published
- 2023
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26. The Relationship between Numbness and Quality of Life.
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Nagai S, Niwa H, Terajima Y, Igari H, Arai YP, Yamashita T, Taguchi T, Nakamura M, and Ushida T
- Abstract
Background: Numbness is a term commonly used in clinical practice to describe an abnormal sensory experience that is produced by a stimulus or is present even without a stimulus. However, there is still much that remains obscure in this field, and also, few reports have focused on its symptoms. In addition, while pain itself is known to have a significant impact on quality of life (QOL), the relationship between numbness and QOL is often unclear. Therefore, we conducted an epidemiological survey and analyzed the relationship between painless numbness and QOL, using type, location, and age as influencing factors, respectively., Methods: A nationwide epidemiological survey was conducted by mail using a survey panel designed by the Nippon Research Center. Questionnaires were sent to 10,000 randomly selected people aged 18 and over from all over Japan. Out of the 5682 people who responded, the relationship between numbness and QOL was analyzed using the EuroQol 5 Dimension-3L (EQ5D-3L) for patients who are currently experiencing painless numbness., Findings: The results suggest that painless numbness affects QOL and that QOL decreases as its intensity increases. Furthermore, the two factors of numbness of feet and numbness among the young may be less likely to affect QOL. This study may be of great significance in the field of numbness research.
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- 2023
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27. Germline variants of IGHV3-53 / V3-66 are determinants of antibody responses to the BNT162b2 mRNA COVID-19 vaccine.
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Mashimo Y, Yamazaki K, Kageyama T, Tanaka S, Taniguchi T, Matsushita K, Igari H, Hanaoka H, Yokote K, Nakajima H, and Onouchi Y
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- Humans, COVID-19 Vaccines, Antibody Formation, RNA, Messenger, Germ Cells, Antibodies, Viral, BNT162 Vaccine, COVID-19 prevention & control
- Abstract
Competing Interests: Declaration of Competing Interest None.
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- 2022
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28. First-in-human autologous implantation of genetically modified adipocytes expressing LCAT for the treatment of familial LCAT deficiency.
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Aso M, Yamamoto TT, Kuroda M, Wada J, Kubota Y, Ishikawa K, Maezawa Y, Teramoto N, Tawada A, Asada S, Aoyagi Y, Kirinashizawa M, Onitake A, Matsuura Y, Yasunaga K, Konno SI, Nishino K, Yamamoto M, Miyoshi J, Kobayashi N, Tanio M, Ikeuchi T, Igari H, Mitsukawa N, Hanaoka H, Yokote K, and Saito Y
- Abstract
Background: Familial lecithin: cholesterol acyltransferase (LCAT) deficiency (FLD) is a severe inherited disease without effective treatment. Patients with FLD develop severe low HDL, corneal opacity, hemolytic anemia, and renal injury., Objective: We developed genetically modified adipocytes (GMAC) secreting LCAT (LCAT-GMAC) for ex vivo gene therapy. GMACs were prepared from the patient's adipocytes to express LCAT by retroviral gene transduction to secrete functional enzymes. This study aimed to evaluate the safety and efficacy of LCAT-GMAC implantation in an FLD patient., Methods: Proliferative preadipocytes were obtained from a patient using a ceiling culture and retrovirally transduced with LCAT. After obtaining enough cells by expansion culture of the transduced cells, the resulting LCAT-GMACs were implanted into a patient with FLD. To evaluate the safety and efficacy, we analyzed the outcome of the autologous implantation for 24 weeks of observation and subsequent 240 weeks of the follow-up periods., Results: This first-in-human autologous implantation of LCAT-GMACs was shown to be safe by evaluating adverse events. The LCAT-GMAC implantation increased serum LCAT activity by approximately 50% of the baseline and sustained over three years. Consistent with increased LCAT activity, intermediate-density lipoprotein (IDL) and free cholesterol levels of the small and very small HDL fractions decreased. We found the hemoglobin/haptoglobin complex in the hemolyzed pre-implantation sera of the patient. After one week of the implantation, the hemoglobin/haptoglobin complex almost disappeared. Immediately after the implantation, the patient's proteinuria decreased temporarily to mild levels and gradually increased to the baseline. At 48 weeks after implantation, the patient's proteinuria deteriorated with the development of mild hypertension. By the treatment with antihypertensives, the patient's blood pressure normalized. With the normalization of blood pressure, the proteinuria rapidly decreased to mild proteinuria levels., Conclusions: LCAT-GMAC implantation in a patient with FLD is shown to be safe and appears to be effective, in part, for treating anemia and proteinuria in FLD., Competing Interests: The authors declare the following conflict of interests: Tokuo Yamamoto is an employee of CellGenTech, Inc. and Chiba University during the study. Masayuki Kuroda reports Joint research funds from CellGenTech, Inc. during the study. The other authors have nothing to disclose., (© 2022 The Author(s).)
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- 2022
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29. Antibody responses and SARS-CoV-2 infection after BNT162b2 mRNA booster vaccination among healthcare workers in Japan.
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Igari H, Asano H, Murata S, Yoshida T, Kawasaki K, Kageyama T, Ikeda K, Koshikawa H, Okuda Y, Urushihara M, Chiba H, Yahaba M, Taniguchi T, Matsushita K, Yoshino I, Yokote K, and Nakajima H
- Subjects
- Adult, Antibodies, Viral, Antibody Formation, BNT162 Vaccine, Health Personnel, Humans, Japan epidemiology, RNA, Messenger, Retrospective Studies, SARS-CoV-2, Vaccination, Young Adult, COVID-19 epidemiology, COVID-19 prevention & control, Vaccines
- Abstract
Introduction: Vaccine effectiveness against SARS-CoV-2 infections decreases due to waning immunity, and booster vaccination was therefore introduced. We estimated the anti-spike antibody (AS-ab) recovery by booster vaccination and analyzed the risk factors for SARS-CoV-2 infections., Methods: The subjects were health care workers (HCWs) in a Chiba University Hospital vaccination cohort. They had received two doses of vaccine (BNT162b2) and a booster vaccine (BNT162b2). We retrospectively analyzed AS-ab titers and watched out for SARS-CoV-2 infection for 90 days following booster vaccination., Results: AS-ab titer eight months after two-dose vaccinations had decreased to as low as 587 U/mL (median, IQR (interquartile range) 360-896). AS-ab titer had then increased to 22471 U/mL (15761-32622) three weeks after booster vaccination. There were no significant differences among age groups. A total of 1708 HCWs were analyzed for SARS-CoV-2 infection, and 48 of them proved positive. SARS-CoV-2 infections in the booster-vaccinated and non-booster groups were 1.8% and 4.0%, respectively, and were not significant. However, when restricted to those 20-29 years old, SARS-CoV-2 infections in the booster-vaccinated and non-booster groups were 2.9% and 13.6%, respectively (p = 0.04). After multivariate logistic regression, COVID-19 wards (adjusted odds ratio (aOR):2.9, 95% confidence interval (CI) 1.5-5.6) and those aged 20-49 years (aOR:9.7, 95%CI 1.3-71.2) were risk factors for SARS-CoV-2 infection., Conclusions: Booster vaccination induced the recovery of AS-ab titers. Risk factors for SARS-CoV-2 infection were HCWs of COVID-19 wards and those aged 20-49 years. Increased vaccination coverage, together with implementing infection control, remains the primary means of preventing HCWs from SARS-CoV-2 infection., Competing Interests: Declaration of competing interest The authors whose names are listed in the manuscript have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
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- 2022
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30. Development of multiplex S-gene-targeted RT-PCR for rapid identification of SARS-CoV-2 variants by extended S-gene target failure.
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Imaizumi Y, Ishige T, Fujikawa T, Miyabe A, Murata S, Kawasaki K, Nishimura M, Taniguchi T, Igari H, and Matsushita K
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- Base Sequence, COVID-19 Testing, Humans, Reverse Transcriptase Polymerase Chain Reaction, COVID-19 diagnosis, SARS-CoV-2 genetics
- Abstract
Background: Tracking SARS-CoV-2 variants of concern (VOC) by genomic sequencing is time-consuming. The rapid screening of VOCs is necessary for clinical laboratories. In this study, we developed a rapid screening method based on multiplex RT-PCR by extended S-gene target failure (eSGTF), a false negative result caused by S-gene mutations., Methods: Three S-gene target (SGT) regions (SGT1, codons 65-72; SGT2, codons 152-159; and SGT3, codons 370-377) and an N-gene region (for internal control) were detected in single-tube. Four types of VOC (Alpha, Delta, Omicron BA.1, and Omicron BA.2) are classified by positive/negative patterns of 3 S-gene regions (eSGTF pattern)., Results: The eSGTF patterns of VOCs were as follows (SGT1, SGT2, SGT3; P, positive; N, negative): Alpha, NPP; Delta, PNP; Omicron BA.1, NPN pattern; and Omicron BA.2, PPN. As compared with the S-gene sequencing, eSGTF patterns were identical to the specific VOCs (concordance rate = 96.7%, N = 206/213). Seven samples with discordant results had a minor mutation in the probe binding region. The epidemics of VOCs estimated by eSGTF patterns were similar to those in Japan., Conclusions: Multiplex RT-PCR and eSGTF patterns enable high-throughput screening of VOCs. It will be useful for the rapid determination of VOCs in clinical laboratories., 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 © 2022 Elsevier B.V. All rights reserved.)
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- 2022
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31. Detecting time-evolving phenotypic components of adverse reactions against BNT162b2 SARS-CoV-2 vaccine via non-negative tensor factorization.
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Ikeda K, Nakada TA, Kageyama T, Tanaka S, Yoshida N, Ishikawa T, Goshima Y, Otaki N, Iwami S, Shimamura T, Taniguchi T, Igari H, Hanaoka H, Yokote K, Tsuyuzaki K, Nakajima H, and Kawakami E
- Abstract
Symptoms of adverse reactions to vaccines evolve over time, but traditional studies have focused only on the frequency and intensity of symptoms. Here, we attempt to extract the dynamic changes in vaccine adverse reaction symptoms as a small number of interpretable components by using non-negative tensor factorization. We recruited healthcare workers who received two doses of the BNT162b2 mRNA COVID-19 vaccine at Chiba University Hospital and collected information on adverse reactions using a smartphone/web-based platform. We analyzed the adverse-reaction data after each dose obtained for 1,516 participants who received two doses of vaccine. The non-negative tensor factorization revealed four time-evolving components that represent typical temporal patterns of adverse reactions for both doses. These components were differently associated with background factors and post-vaccine antibody titers. These results demonstrate that complex adverse reactions against vaccines can be explained by a limited number of time-evolving components identified by tensor factorization., Competing Interests: The authors have no competing interests to declare., (© 2022 The Authors.)
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- 2022
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32. Elevated Myl9 reflects the Myl9-containing microthrombi in SARS-CoV-2-induced lung exudative vasculitis and predicts COVID-19 severity.
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Iwamura C, Hirahara K, Kiuchi M, Ikehara S, Azuma K, Shimada T, Kuriyama S, Ohki S, Yamamoto E, Inaba Y, Shiko Y, Aoki A, Kokubo K, Hirasawa R, Hishiya T, Tsuji K, Nagaoka T, Ishikawa S, Kojima A, Mito H, Hase R, Kasahara Y, Kuriyama N, Tsukamoto T, Nakamura S, Urushibara T, Kaneda S, Sakao S, Tobiume M, Suzuki Y, Tsujiwaki M, Kubo T, Hasegawa T, Nakase H, Nishida O, Takahashi K, Baba K, Iizumi Y, Okazaki T, Kimura MY, Yoshino I, Igari H, Nakajima H, Suzuki T, Hanaoka H, Nakada TA, Ikehara Y, Yokote K, and Nakayama T
- Subjects
- Humans, Leukocytes, Mononuclear, RNA-Seq, Single-Cell Analysis, Spectrometry, X-Ray Emission, COVID-19 blood, COVID-19 complications, COVID-19 pathology, Lung blood supply, Lung metabolism, Lung pathology, Lung virology, Myosin Light Chains blood, SARS-CoV-2 isolation & purification, Severity of Illness Index, Thromboinflammation pathology, Thromboinflammation virology, Vasculitis pathology, Vasculitis virology
- Abstract
The mortality of coronavirus disease 2019 (COVID-19) is strongly correlated with pulmonary vascular pathology accompanied by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-triggered immune dysregulation and aberrant activation of platelets. We combined histological analyses using field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy analyses of the lungs from autopsy samples and single-cell RNA sequencing of peripheral blood mononuclear cells to investigate the pathogenesis of vasculitis and immunothrombosis in COVID-19. We found that SARS-CoV-2 accumulated in the pulmonary vessels, causing exudative vasculitis accompanied by the emergence of thrombospondin-1-expressing noncanonical monocytes and the formation of myosin light chain 9 (Myl9)-containing microthrombi in the lung of COVID-19 patients with fatal disease. The amount of plasma Myl9 in COVID-19 was correlated with the clinical severity, and measuring plasma Myl9 together with other markers allowed us to predict the severity of the disease more accurately. This study provides detailed insight into the pathogenesis of vasculitis and immunothrombosis, which may lead to optimal medical treatment for COVID-19.
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- 2022
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33. Clinical Outcomes of Sotrovimab Treatment in 10 High-Risk Patients with Mild COVID-19: A Case Series.
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Takeda K, Kasai H, Sakao S, Saito M, Shikano K, Naito A, Abe M, Kawasaki T, Yahaba M, Taniguchi T, Igari H, and Suzuki T
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- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antibodies, Neutralizing, Humans, Middle Aged, SARS-CoV-2, COVID-19
- Abstract
BACKGROUND Although sotrovimab reduces the risk of hospitalization or death due to COVID-19, there have been few reports of its use in clinical practice. Particularly, information on the effectiveness of sotrovimab against the omicron variant of the virus is limited. We present 10 cases of COVID-19 treated with sotrovimab at our unit between December 2021 and February 2022. CASE REPORT The age of the patients ranged from 32 to 81 years (median: 40 years). The comorbidities included lung cancer, cardiovascular disease, chronic kidney disease requiring hemodialysis, and AIDS. Two of the patients were also organ recipients. Oxygen saturation (SpO2) was above 97% in all patients. None of the patients presented with pneumonia on admission. However, blood test results showed that all patients had risk factors for severe COVID-19 outcomes. The interval from symptom onset to sotrovimab administration and resolution ranged from 2 to 5 days (median: 2 days) and 2 to 15 days (median: 5 days), respectively. Only 1 patient developed pneumonia and was treated with remdesivir after sotrovimab administration. However, this patient did not require oxygen therapy. Although no moderate to severe adverse events were observed, a mild adverse event was observed in 1 patient. CONCLUSIONS Sotrovimab could be safe and effective in preventing progression of COVID-19 in patients with a variety of underlying diseases and who are at high risk of severe disease outcomes.
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- 2022
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34. COVID-19 infection control education for medical students undergoing clinical clerkship: a mixed-method approach.
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Kasai H, Saito G, Ito S, Kuriyama A, Kawame C, Shikino K, Takeda K, Yahaba M, Taniguchi T, Igari H, Sakao S, and Suzuki T
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- Humans, Infection Control, Personal Protective Equipment, COVID-19 prevention & control, Clinical Clerkship, Students, Medical
- Abstract
Background: Coronavirus disease (COVID-19) has induced an urgent need to train medical students not only in infection prevention control but also in the treatment of infectious diseases, including COVID-19. This study evaluates the impact of simulated clinical practice with peer role-plays and a lecture on clinical education for COVID-19., Methods: The sample for the study included 82 fourth- and fifth-year medical students undergoing clinical clerkship in respiratory medicine. They answered questionnaires and participated in semi-structured focus group interviews (FGIs) regarding the advantages of simulated clinical practice with peer role-plays and lectures on clinical education for COVID-19., Results: A total of 75 students participated in the COVID-19 education program between January and November 2021. The responses to the questionnaire revealed that the satisfaction level of students with COVID-19 education was high. No significant change was found among students concerning fear of COVID-19 before and after the program. The degree of burden of handling information on COVID-19 reduced significantly, while the degree with respect to the use of personal protective equipment (PPE), including appropriate wearing and removing of PPE, and care of patients with confirmed COVID-19 while taking steps to prevent infection, exhibited a decreasing trend. Nine FGIs were conducted (n = 74). The advantages of simulated clinical practice were segregated into five categories (infection prevention control, educational methods, burden on healthcare providers, self-reflection, and fear of COVID-19); and that of the lecture were segregated into four categories (information literacy, knowledge of COVID-19, educational methods, and self-reflection)., Conclusions: Simulated clinical practice with peer role-plays and the lecture pertaining to COVID-19 can prove to be efficient and safe methods for learning about COVID-19 infection and prevention control for medical students. They can reduce the burden of COVID-19 patients' care. Moreover, they can also provide an opportunity for self-reflection, realize the burden of medical care, and acquire relevant information., (© 2022. The Author(s).)
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- 2022
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35. Clinical characteristics and treatment outcomes of carbapenem-resistant Enterobacterales infections in Japan.
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Oka K, Matsumoto A, Tetsuka N, Morioka H, Iguchi M, Ishiguro N, Nagamori T, Takahashi S, Saito N, Tokuda K, Igari H, Fujikura Y, Kato H, Kanai S, Kusama F, Iwasaki H, Furuhashi K, Baba H, Nagao M, Nakanishi M, Kasahara K, Kakeya H, Chikumi H, Ohge H, Azuma M, Tauchi H, Shimono N, Hamada Y, Takajo I, Nakata H, Kawamura H, Fujita J, and Yagi T
- Subjects
- Humans, Carbapenems pharmacology, Carbapenems therapeutic use, Japan epidemiology, Retrospective Studies, Treatment Outcome, Carbapenem-Resistant Enterobacteriaceae genetics, Enterobacteriaceae Infections drug therapy, Enterobacteriaceae Infections epidemiology, Sepsis
- Abstract
Objectives: The dissemination of difficult-to-treat carbapenem-resistant Enterobacterales (CRE) is of great concern. We clarified the risk factors underlying CRE infection mortality in Japan., Methods: We conducted a retrospective, multicentre, observational cohort study of patients with CRE infections at 28 university hospitals from September 2014 to December 2016, using the Japanese National Surveillance criteria. Clinical information, including patient background, type of infection, antibiotic treatment, and treatment outcome, was collected. The carbapenemase genotype was determined using PCR sequencing. Multivariate analysis was performed to identify the risk factors for 28-day mortality., Results: Among the 179 patients enrolled, 65 patients (36.3%) had bloodstream infections, with 37 (20.7%) infections occurring due to carbapenemase-producing Enterobacterales (CPE); all carbapenemases were of IMP-type (IMP-1: 32, IMP-6: 5). Two-thirds of CPE were identified as Enterobacter cloacae complex. Combination therapy was administered only in 46 patients (25.7%), and the 28-day mortality rate was 14.3%. Univariate analysis showed that solid metastatic cancer, Charlson Comorbidity Index ≥3, bloodstream infection, pneumonia, or empyema, central venous catheters, mechanical ventilation, and prior use of quinolones were significant risk factors for mortality. Multivariate analysis revealed that mechanical ventilation (OR: 6.71 [1.42-31.6], P = 0.016), solid metastatic cancers (OR: 5.63 [1.38-23.0], P = 0.016), and bloodstream infections (OR: 3.49 [1.02-12.0], P = 0.046) were independent risk factors for 28-day mortality., Conclusion: The significant risk factors for 28-day mortality in patients with CRE infections in Japan are mechanical ventilation, solid metastatic cancers, and bloodstream infections., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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36. Adverse effect investigation using application software after vaccination against SARS-CoV-2 for healthcare workers.
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Yamazaki S, Watanabe K, Okuda Y, Urushihara M, Koshikawa H, Chiba H, Yahaba M, Taniguchi T, Nakada TA, Nakajima H, Ishii I, and Igari H
- Subjects
- Health Personnel, Humans, SARS-CoV-2, Software, Vaccination adverse effects, COVID-19 prevention & control, COVID-19 Vaccines adverse effects, Drug-Related Side Effects and Adverse Reactions
- Abstract
Introduction: The usefulness of smartphone-based application software as a way to manage adverse events (AEs) after vaccination is well known. The purpose of this study is to clarify the usefulness and precautions of employing a smartphone application for collecting AEs after the administration of Comirnaty®️., Methods: Healthcare workers (HCWs) who were vaccinated with Comirnaty®️ were asked to register for the application software and to report AEs for 14 days after vaccination. AEs were self-reported according to severity. The software was set to output an alert in case of fever., Results: The number of HCWs who received the first dose was 2,551, and 2,406 (94.3%) reported their vaccinations. 2,547 received the second dose, and 2,347 (92.1%) reported their vaccinations. With the first dose, the reporting rate stayed above 83.3% until the final day. On the other hand, that of the second dose decreased rapidly after 6 days. The most frequent symptom was "pain at injection site" (more than 70%). Severe AEs were 6.6% after the second dose, with 0.6% visiting a clinic. Many AEs peaked on the day after administration and disappeared within 1 week. There were few reports of fever., Conclusion: Smartphone applications can be used to collect information on AEs after vaccination. Application settings and dissemination are necessary to maintain the reporting rate of HCWs., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
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- 2022
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37. Tracking SARS-CoV-2 variants by entire S-gene analysis using long-range RT-PCR and Sanger sequencing.
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Matsubara M, Imaizumi Y, Fujikawa T, Ishige T, Nishimura M, Miyabe A, Murata S, Kawasaki K, Taniguchi T, Igari H, and Matsushita K
- Subjects
- Humans, Mutation, Reverse Transcriptase Polymerase Chain Reaction, COVID-19 diagnosis, SARS-CoV-2 genetics
- Abstract
Introduction: Genomic surveillance of the SARS-CoV-2 virus is important to assess transmissibility, disease severity, and vaccine effectiveness. The SARS-CoV-2 genome consists of approximately 30 kb single-stranded RNA that is too large to analyze the whole genome by Sanger sequencing. Thus, in this study, we performed Sanger sequencing following long-range RT-PCR of the entire SARS-CoV-2 S-gene and analyzed the mutational dynamics., Methods: The 4 kb region, including the S-gene, was amplified by two-step long-range RT-PCR. Then, the entire S-gene sequence was determined by Sanger sequencing. The amino acid mutations were identified as compared with the reference SARS-CoV-2 genome., Results: The S:D614G mutation was found in all samples. The R.1 variants were detected after January 2021. Alpha variants started to emerge in April 2021. Delta variants replaced Alpha in July 2021. Then, Omicron variants were detected after December 2021. These mutational dynamics in samples collected in the Chiba University Hospital were similar to those in Japan., Conclusion: The emergence of variants of concern (VOC) has been reported by the entire S-gene analysis. As the VOCs have unique mutational patterns of the S-gene region, analysis of the entire S-gene will be useful for molecular surveillance of the SARS-CoV-2 in clinical laboratories., (Copyright © 2022 Elsevier B.V. All rights reserved.)
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- 2022
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38. Tolerability of prone positioning in non-intubated patients with hypoxaemia due to COVID-19-related pneumonia.
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Shikano K, Sakao S, Inaba Y, Taniguchi T, Saito G, Naito A, Abe M, Kasai H, Yahaba M, Kawasaki T, Shigeta A, Ikari J, Sugiura T, Kawasaki Y, Igari H, and Suzuki T
- Subjects
- Humans, Hypoxia etiology, Hypoxia therapy, Patient Positioning adverse effects, Prone Position, COVID-19 complications, Respiratory Insufficiency
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- 2022
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39. Immunological features that associate with the strength of antibody responses to BNT162b2 mRNA vaccine against SARS-CoV-2.
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Kageyama T, Tanaka S, Etori K, Hattori K, Miyachi K, Kasuya T, Iwamoto T, Ikeda K, Igari H, Yokote K, and Nakajima H
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- Antibodies, Viral, Antibody Formation, CD8-Positive T-Lymphocytes, COVID-19 Vaccines, Humans, Leukocytes, Mononuclear, SARS-CoV-2, Vaccines, Synthetic, mRNA Vaccines, BNT162 Vaccine, COVID-19 prevention & control
- Abstract
Predictive clinical factors associated with favorable responses to BNT162b2 mRNA vaccine against SARS-CoV-2 have been reported in some studies; however, there is a subgroup with low antibodytiters without well-known clinical factors reducing antibody responses. To clarify the immunological backgrounds that underlie the difference in antibody responses, we analyzed peripheral blood mononuclear cells (PBMCs) of each 20 individuals with a high anti-SARS-CoV-2 antibody titer and a low antibody titer out of 1774 healthcare workers who received BNT162b2 mRNA vaccine. A higher percentage of B cells before vaccination was associated with a higher antibody titer. Among B cells, naïve and transitional B cell frequencies were positively correlated with a higher antibody titer, whereas the frequencies of late memory B cells and plasmablasts were associated with a lower antibody titer. Fold change in the frequency of activated CD8
+ T cells upon vaccination was also correlated with high antibody titers., 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 © 2022 Elsevier Ltd. All rights reserved.)- Published
- 2022
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40. Efficient automated semi-quantitative urine culture analysis via BD Urine Culture App.
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Uwamino Y, Nagata M, Aoki W, Kato A, Daigo M, Ishihara O, Igari H, Inose R, Hasegawa N, and Murata M
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- Automation, Bacteriological Techniques methods, Urinalysis methods, Urine microbiology
- Abstract
We aimed to assess the clinical utility of BD Kiestra
TM Urine Culture App (UCA). High concordance rates were observed between the urine culture colony counts obtained by medical technologists and those produced using UCA. This application may increase the efficiency of obtaining semi-quantitative urine culture results., Competing Interests: Declaration of competing interest Beckton Dickinson is a developer and distributor of BD Kiestra(TM) Solutions and BD Urine Culture App., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2022
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41. Antibody responses to BNT162b2 mRNA COVID-19 vaccine and their predictors among healthcare workers in a tertiary referral hospital in Japan.
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Kageyama T, Ikeda K, Tanaka S, Taniguchi T, Igari H, Onouchi Y, Kaneda A, Matsushita K, Hanaoka H, Nakada TA, Ohtori S, Yoshino I, Matsubara H, Nakayama T, Yokote K, and Nakajima H
- Subjects
- Adult, Antibodies, Viral blood, Female, Humans, Japan, Male, Tertiary Care Centers, Antibody Formation, BNT162 Vaccine immunology, COVID-19 prevention & control, Health Personnel
- Abstract
Objectives: This study aimed to determine antibody responses in healthcare workers who receive the BNT162b2 mRNA COVID-19 vaccine and identify factors that predict the response., Methods: We recruited healthcare workers receiving the BNT162b2 mRNA COVID-19 vaccine at the Chiba University Hospital COVID-19 Vaccine Center. Blood samples were obtained before the 1st dose and after the 2nd dose vaccination, and serum antibody titers were determined using Elecsys® Anti-SARS-CoV-2S, an electrochemiluminescence immunoassay. We established a model to identify the baseline factors predicting post-vaccine antibody titers using univariate and multivariate linear regression analyses., Results: Two thousand fifteen individuals (median age 37-year-old, 64.3% female) were enrolled in this study, of which 10 had a history of COVID-19. Before vaccination, 21 participants (1.1%) had a detectable antibody titer (≥0.4 U/mL) with a median titer of 35.9 U/mL (interquartile range [IQR] 7.8 - 65.7). After vaccination, serum anti-SARS-CoV-2S antibodies (≥0.4 U/mL) were detected in all 1774 participants who received the 2nd dose with a median titer of 2060.0 U/mL (IQR 1250.0 - 2650.0). Immunosuppressive medication (p < 0.001), age (p < 0.001), time from 2nd dose to sample collection (p < 0.001), glucocorticoids (p = 0.020), and drinking alcohol (p = 0.037) were identified as factors predicting lower antibody titers after vaccination, whereas previous COVID-19 (p < 0.001), female (p < 0.001), time between 2 doses (p < 0.001), and medication for allergy (p = 0.024) were identified as factors predicting higher serum antibody titers., Conclusions: Our data demonstrate that healthcare workers universally have good antibody responses to the BNT162b2 mRNA COVID-19 vaccine. The predictive factors identified in our study may help optimize the vaccination strategy., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
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- 2021
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42. Possibility of deterioration of respiratory status when steroids precede antiviral drugs in patients with COVID-19 pneumonia: A retrospective study.
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Shionoya Y, Taniguchi T, Kasai H, Sakuma N, Imai S, Shikano K, Takayanagi S, Yahaba M, Nakada TA, Igari H, Sakao S, and Suzuki T
- Subjects
- Aged, Antiviral Agents administration & dosage, COVID-19 physiopathology, COVID-19 virology, Dexamethasone administration & dosage, Drug Administration Schedule, Female, Glucocorticoids administration & dosage, Glucocorticoids therapeutic use, Hospital Mortality, Humans, Intensive Care Units statistics & numerical data, Kaplan-Meier Estimate, Male, Middle Aged, Respiratory Distress Syndrome physiopathology, Retrospective Studies, SARS-CoV-2 physiology, Severity of Illness Index, Treatment Outcome, Antiviral Agents therapeutic use, Dexamethasone therapeutic use, Hospitalization statistics & numerical data, Respiratory Distress Syndrome drug therapy, SARS-CoV-2 drug effects, COVID-19 Drug Treatment
- Abstract
Introduction: Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. Although most patients with COVID-19 develop asymptomatic or mild disease, some patients develop severe disease. The effectiveness of various therapeutic agents, including antiviral drugs, steroids, and anti-inflammatories for COVID-19, have been being confirmed. The effect of administering steroids in early disease is unclear. This study therefore aimed to evaluate the effectiveness and risk of exacerbation of steroids administered preceding antiviral drugs in patients with COVID-19 pneumonia., Methods: This retrospective, single-center, observational study included consecutive patients with COVID-19 between March 2020 and March 2021. Patients were divided into a steroids-first group and antiviral-drugs-first group. Mortality, duration of hospitalization, incidence rate and duration of intensive care unit (ICU) admission, intubation, and extracorporeal membrane oxygenation (ECMO) induction of the two groups were compared., Results: A total of 258 patients were admitted during the study period. After excluding patients who received symptomatic treatment only, who were taking immunosuppressive drugs, or who were administered antiviral drugs only, 68 patients were included in the analysis, 16 in the steroids-first group and 52 in the antiviral-drugs-first group. The rate of intubation, ICU admission and ECMO induction were significantly higher in the steroids-first group than in the antiviral-drugs-first group (81.3% vs. 33.3, p<0.001, 75.0% vs. 29.4%, p = 0.001, and 31.3% vs. 7.8%, p = 0.017, respectively). Furthermore, patients who received steroids within ten days after starting antiviral drugs had significantly lower rates of ICU admission, intubation, and ECMO induction. (81.3% vs. 42.9% p = 0.011, 75.0% vs. 37.1% p = 0.012, and 31.3% vs. 8.6% p = 0.039, respectively)., Conclusions: Administering steroids prior to antiviral drugs soon after symptom onset can aggravate disease severity. When administration of steroids is considered soon after symptom onset, it may be safer to initiate antiviral drugs first., Competing Interests: T.T. has received honorarium for lecture from Gilead Sciences Inc., Janssen Pharmaceuticals Inc., ViiV Healthcare Limited, and MSD Limited, respectively. T.T. is the member of advisory board of Janssen Pharmaceuticals Inc., ViiV Healthcare Limited, and MSD Limited, respectively. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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- 2021
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43. Three-day regimen of oseltamivir for post-exposure prophylaxis of influenza in hospital wards: a study protocol for a prospective, multi-center, single-arm trial.
- Author
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Ishiguro N, Ito YM, Iwasaki S, Nagao M, Kawamura H, Kanai S, Nukui Y, Tokuda K, Miyara T, Igari H, Yamada K, Chikumi H, Sano C, Koike R, Yagi T, and Murakami N
- Subjects
- Adult, Antiviral Agents therapeutic use, Child, Hospitals, Humans, Post-Exposure Prophylaxis, Prospective Studies, Influenza, Human drug therapy, Influenza, Human prevention & control, Oseltamivir therapeutic use
- Abstract
Background: In a previous retrospective observational study, a 3-day regimen of oseltamivir as post-exposure prophylaxis (PEP) for preventing transmission of influenza in wards was shown to be comparable to 7- to 10-day regimens provided index cases were immediately separated from close contacts. In order to confirm the efficacy of a 3-day regimen, we started to conduct a prospective, multi-center, single-arm trial., Methods: This study is a prospective, multi-center, single-arm study designed by the Sectional Meeting of Clinical Study, Japan Infection Prevention and Control Conference for National and Public University Hospitals. Index patients with influenza are prescribed a neuraminidase inhibitor and are discharged immediately or transferred to isolation rooms. The close contacts are given oseltamivir as 75 mg capsules once daily for adults or 2 mg/kg (maximum of 75 mg) once daily for children for 3 days as PEP. All close contacts are monitored for development of influenza for 7 days after starting PEP., Discussion: A 3-day regimen of oseltamivir as PEP has advantages over 7- to 10-day regimens in terms of costs, medication adherence and adverse effects. Trial registration The Institutional Review Board of Hokkaido University Hospital for Clinical Research, 015-0518, registered on November 11, 2016. UMIN Clinical Trials Registry, UMIN000024458, disclosed on October 31, 2016. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027881 . Japan Registry of Clinical Trials, jRCTs011180015, disclosed on March 14, 2019. https://jrct.niph.go.jp/latest-detail/jRCTs011180015., (© 2021. The Author(s).)
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- 2021
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44. Antibiotics prescriptions for pneumonia analyzed by claim information in Japan.
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Yamazaki S, Yamagishi K, Murata S, Yokoyama I, Yahaba M, Takayanagi S, Kawasaki Y, Taniguchi T, Ishii I, and Igari H
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- Adolescent, Adult, Aged, Anti-Bacterial Agents therapeutic use, Humans, Japan, Middle Aged, Prescriptions, Young Adult, Community-Acquired Infections drug therapy, Pneumonia drug therapy
- Abstract
Objective: Japan is an aging society, and pneumonia is the leading cause of death, but the suitability of antibiotics for treating community-acquired pneumonia (CAP) in Japan is not clear. The purpose of this study was to investigate antibacterial drugs for treating CAP according to age., Materials and Methods: Using the Japanese national database from 2011 to 2014, we analyzed the usage of antibiotics for CAP according to age., Results: The numbers of claim information were 9,386, and 70% of the patients were aged ≥ 75 years. Sulbactam/ampicillin (SBT/ABPC) or ceftriaxone (CTRX) was used in 60%, but broad-spectrum antibiotics, combination therapy, and anti-mycoplasma antibiotics were used in 15 - 28% of all age groups. The 30-day survival rate did not differ between SBT/ABPC or CTRX vs. others. There was no difference in 30-day mortality and risk in any group between the ages of 15 and 64 years. On the other hand, the use of anti-mycoplasma antibiotics reduced the 30-day mortality by 0.50 times (p < 0.01), and the use of two or more antibiotics increased the 30-day mortality by 1.45 times (p = 0.02) at age ≥ 65 years., Conclusion: Approximately half of the antibiotics used for CAP requiring hospitalization consisted of CTRX or SBT/ABPC as recommended by the Japanese Respiratory Society (JRS) guidelines. On the other hand, the usage of broad-spectrum antibiotics and combination therapy were relatively frequent at all ages, although their use does not always contribute to survival. Our data provide basic information for analyzing the outcome of pneumonia treatment in terms of an antimicrobial resistance action plan in Japan.
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- 2021
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45. Prevalence of positive IGRAs and innate immune system in HIV-infected individuals in Japan.
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Igari H, Takayanagi S, Yahaba M, Tsuyuzaki M, Taniguchi T, and Suzuki K
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- CD8-Positive T-Lymphocytes, Humans, Interferon-gamma Release Tests, Japan epidemiology, Middle Aged, Prevalence, Tuberculin Test, HIV Infections drug therapy, HIV Infections epidemiology, Latent Tuberculosis, Mycobacterium tuberculosis
- Abstract
Introduction: Human immunodeficiency virus (HIV) infected individuals are at increased risk of developing active tuberculosis (TB). TB incidence remains higher than in non-HIV subjects after antiretroviral therapy (ART) initiation. This study was conducted to estimate the prevalence of positive IGRA, reflecting latent tuberculosis infection and/or a history of active TB, in HIV-infected individuals after ART initiation in Japan., Methods: Two IGRAs (Interferon (IFN)-γ release assays), QuantiFERON®-TB Gold Plus (QFT-Plus) and T-Spot®.TB (TSPOT), were used. We also analyzed the TB associated risk factors for the IGRAs results and the role of CD4
+ T-cells, CD8+ T-cells and NK cells for producing IFN-γ. We also analyzed the risk factors for positive IGRA responses and the role of CD4+ T-cells, CD8+ T-cells and NK cells for producing IFN-γ., Results: One hundred eight-four subjects were prospectively enrolled. Median age was 49 years. The positivity rates of QFT-Plus and TSPOT were 7.6% [95%CI 4.6-12.4] and 2.7% [95%CI 1.2-6.2], respectively, with significant difference. TB-associated risk factors and NK cells ≥300/μL were selected as independently significant factors by multivariate logistic regression. The NK cell count revealed significant linear regression with IFN-γ production responding to TB-specific antigens., Conclusions: The prevalence of positive IGRAs was 2.7%-7.6%. QFT-Plus would be practical for a higher positivity rate and reflect TB risk factors. The innate immune system, referring to IFN-γ production, plays an important role in the immune response to TB-specific antigens even after initiating ART., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020. Published by Elsevier Ltd.)- Published
- 2021
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46. Drug Fever Due to Favipiravir Administration for the Treatment of a COVID-19 Patient.
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Tawara J, Uehara T, Sakao S, Igari H, Taniguchi T, Kasai H, Takayanagi S, Yahaba M, Shimada R, and Ikusaka M
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- Amides, Antiviral Agents adverse effects, Fever chemically induced, Humans, Male, Middle Aged, Pyrazines, SARS-CoV-2, COVID-19, Pharmaceutical Preparations
- Abstract
A 55-year-old Japanese man was hospitalized with the novel coronavirus disease 2019 (COVID-19). On the 14th day after the start of favipiravir administration, the patient developed a fever with a temperature of 38.1°C. His pulse rate also became elevated to 128 bpm, so relative bradycardia was not suspected. Since he was in good overall health and no concomitant symptoms and signs were apparent, we considered it to be drug fever due to favipiravir. After the completion of favipiravir treatment, the patient's temperature normalized within 24 hours. We herein report this case of drug fever caused by favipiravir.
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- 2021
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47. Antibiotics for hospitalized children with community-acquired pneumonia in Japan: Analysis based on Japanese national database.
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Yahaba M, Yamagishi K, Yamazaki S, Takayanagi S, Kawasaki Y, Taniguchi T, Ishiwada N, and Igari H
- Subjects
- Anti-Bacterial Agents therapeutic use, Child, Child, Hospitalized, Humans, Infant, Japan epidemiology, Community-Acquired Infections drug therapy, Community-Acquired Infections epidemiology, Pneumonia drug therapy, Pneumonia epidemiology, Pneumonia, Bacterial drug therapy
- Abstract
Introduction: Community-acquired pneumonia (CAP) is one of the most common causes of pediatric infection requiring hospitalization. Antimicrobial resistance due to the inappropriate use poses a threat worldwide. Our objective is to analyze and optimize the trends of antibiotics used for pediatric inpatients with CAP in a claims database provided by the Ministry of Health, Labour and Welfare., Methods: Our database randomly sampled 10% of the hospitalized patients every October from 2011 to 2014. Patients aged <15 years in whom antibiotic therapy was initiated within two days of admission were listed. Subsequently, we investigated the antibiotics administered on the first day of prescription., Results: A total of 4,831 antibiotics were prescribed for 3,909 patients. Many patients aged ≤ five years were treated with β-lactams alone whereas many patients aged ≥ six years were treated with a single antibiotic, such as a macrolide, tetracycline, and quinolone, which covers atypical bacteria. Combination therapy was primarily used in children aged ≥ six years (nearly 30%); the main combination was a β-lactam and non-β-lactam covering atypical bacteria. Ampicillin-sulbactam was the most frequently prescribed β-lactam in children of all ages other than infants. Ampicillin, however, was most often prescribed in infants, but its usage rate was low at other ages., Conclusions: Antibiotics were appropriately prescribed and were similar to that recommended in the 2011 guidelines for pediatric inpatients with CAP. However, combination therapy was frequently prescribed in children aged ≥ six years. According to the revised guidelines in 2017, ampicillin should be used more frequently for patients hospitalized with CAP., (Copyright © 2020. Published by Elsevier Ltd.)
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- 2021
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48. Suspected cholestatic liver injury induced by favipiravir in a patient with COVID-19.
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Yamazaki S, Suzuki T, Sayama M, Nakada TA, Igari H, and Ishii I
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- Aged, Amides therapeutic use, Antiviral Agents therapeutic use, COVID-19 complications, Drug Therapy, Combination, Extracorporeal Membrane Oxygenation, Humans, Lopinavir therapeutic use, Male, Pyrazines therapeutic use, Ritonavir therapeutic use, SARS-CoV-2, Amides adverse effects, Antiviral Agents adverse effects, Chemical and Drug Induced Liver Injury etiology, Cholestasis etiology, Pyrazines adverse effects, COVID-19 Drug Treatment
- Abstract
Favipiravir is an antiviral drug that is expected to have a therapeutic effect on SARS-CoV2 infection. Teratogenicity and hyperuricemia are known as the main side effects of favipiravir, but little is known about other side effects. This report describes a case of cholestatic liver injury induced by favipiravir. A 73-year-old Japanese with a history of alcoholic hepatitis was infected with SARS-CoV2. Drug therapy was instituted with lopinavir/ritonavir combined with interferon β-1b. However, his condition worsened despite additional support with continuous hemodiafiltration and veno-venous extracorporeal membrane oxygenation. We suspected complications of bacterial pneumonia and started favipiravir in addition to antimicrobial therapy. Favipiravir was administered at 6000 mg/day on the first day and 2400 mg/day for the second and subsequent days for 14 days. After the initiation of antibiotics, transaminase and total bilirubin were elevated, suggesting a transient cholestasic liver dysfunction. The liver dysfunction in this case may have been triggered by antibacterial treatment, and high dose of favipiravir may have promoted the deterioration of liver function. Monitoring of liver function is vital and close attention should be paid when using favipiravir at high doses or in patients with impaired liver function., Competing Interests: Declaration of competing interest None of the authors report any conflict of interest. We have not received any financial support for this report., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
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- 2021
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49. A structured summary of a study protocol for a multi-center, randomized controlled trial (RCT) of COVID-19 prevention with Kampo medicines (Integrative Management in Japan for Epidemic Disease by prophylactic study: IMJEDI P1 study).
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Namiki T, Takayama S, Arita R, Ishii T, Kainuma M, Makino T, Mimura M, Yoshino T, Nogami T, Arai M, Sato J, Tanaka K, Nakae H, Igari H, Ozawa Y, Shiko Y, Kawasaki Y, Nezu M, and Ito T
- Subjects
- Administration, Oral, Adult, Aged, COVID-19 diagnosis, COVID-19 epidemiology, COVID-19 virology, COVID-19 Nucleic Acid Testing, Drug Administration Schedule, Drugs, Chinese Herbal adverse effects, Female, Humans, Japan epidemiology, Male, Medicine, Kampo adverse effects, Middle Aged, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Risk Factors, Severity of Illness Index, Treatment Outcome, Young Adult, COVID-19 prevention & control, Drugs, Chinese Herbal administration & dosage, Medicine, Kampo methods, Pandemics prevention & control, SARS-CoV-2 isolation & purification
- Abstract
Objective: We aimed to test our hypothesis that traditional Japanese (Kampo) medicine, hochuekkito (Hochu-ekki-to: HET) has a preventive effect for the symptoms on COVID-19., Trial Design: The study is designed as a multi-center, interventional, parallel-group, randomized (1:1 ratio), investigator sponsored, two-arm study., Participants: Six thousand participants will be recruited from healthy hospital workers in 7 Japanese University Hospitals., Inclusion Criteria: 1. Age from 20 to 75 years old at the time of registration 2. Asymptomatic and body temperature below 37°C at the time of registration 3. Capable of eating orally Exclusion criteria: 1. Previous upper respiratory inflammation due to viral infection (including suspected COVID-19) 2. Taking immunosuppressants 3. Allergic to the Kampo medicines used in this study 4. History of hypokalaemia, severe hypertension, severe liver dysfunction, and interstitial pneumonia 5. Regularly taking other Kampo medicines 6. Pregnant or possibly pregnant 7. Participating in other research 8. Judged to be unsuitable for this study by the doctor in charge INTERVENTION AND COMPARATOR: Kampo group: participants receive HET in 9 tablets 2 times per day for 8 weeks., Control Group: participants receive placebo in the same dosage as the Intervention group - 9 tablets 2 times per day for 8 weeks. Placebo tablets are identical in appearance and package to HET. Taste of placebo is different from that of HET. The Ohsugi Pharmaceutical Co. Ltd, Osaka, Japan manufactured the placebo and HET., Main Outcomes: Primary outcome: Number of patients with a SARS-CoV-2 RNA by ploymerase chain reaction (PCR) positive result with at least one symptom (fever, cough, sputum, malaise, shortness of breath) during the 12-week study period (including the 4-week observation period after oral administration)., Secondary Outcomes: 1. Period from infection to onset 2. Period from the appearance of symptoms to the disappearance of PCR positive 3. Number of days until the appearance or improvement of symptoms 4. Severe stage: presence of hospitalization 5. Shock stage: ICU management required for mechanical ventilation, shock vitals or failure of organ(s) other than lungs Safety endpoints include numbness in the hands and/or feet, edema, skin rash or other allergic symptoms, and gastric discomfort., Randomisation: Patients are randomized (1:1 ratio) to each group using minimization implemented with the Electric data capture system (DATATRAK Enterprise Cloud), with balancing of the arms with age range (under 50 years of age or not) and having a history of risk factors for COVID-19 (cardiovascular disease, hypertension, diabetes, respiratory diseases)., Blinding (masking): Only participants will be randomized., Numbers to Be Randomised (sample Size): The main research hypothesis of this study is that Kampo medicines significantly prevent the onset of COVID-19. It is assumed that the infection rate before the administration of the drug under consideration will be 0% and that the incidence of COVID-19 thereafter will be 2- 3%, of which 70%-80% will show symptoms of COVID-19. Assuming that the pharmaceutical effect of the drug will be effective in 50% of patients and that the incidence rates in the placebo and drug groups will be 1.4%-2.4% and 0.7%-1.2%, respectively, the placebo is calculated at 2%, and the study drug at 1%. Since the frequency of verification is low and the number of cases will be large, we set a total of 10 analyses (9 interim analyses and a final analysis). Since the number of cases at the time of the final analysis will be 4,986 under the conditions of α = 0.05 and a power of 80% by the Peto method. We set at 600 cases in each interim analysis with an estimated dropout rate of 16.9%. Finally, the total number of cases is set to 6,000 with 3,000 in the placebo group and 3,000 in the HET group., Trial Status: Protocol version 1.3 of October 23rd , 2020. Recruitment start (expected): December 1
st , 2020. Recruitment finish (expected): December 31st , 2022., Trial Registration: This trial is registered in the Japan Registry of Clinical Trials (jRCT) ( jRCTs031200150 ) on 14 October 2020., Full Protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.- Published
- 2021
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50. Clinical course of a critically ill patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
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Takahashi N, Abe R, Hattori N, Matsumura Y, Oshima T, Taniguchi T, Igari H, and Nakada TA
- Subjects
- Aged, COVID-19, Disease Progression, Humans, Male, SARS-CoV-2, Betacoronavirus, Coronavirus Infections epidemiology, Critical Illness epidemiology, Pandemics, Pneumonia, Viral epidemiology
- Abstract
Although several studies have reported on the clinical and epidemiological characteristics of the patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinical course of the most severe cases requiring treatment in ICU have been insufficiently reported. A 73-year-old man traveling on a cruise ship with history of hypertension and dyslipidemia developed high fever, dyspnea and cough after 7 days of steroid treatment for sudden sensorineural hearing loss, and tested positive for SARS-CoV-2 in sputa polymerase chain reaction (PCR) examination. His respiratory function deteriorated despite treatments with lopinavir/ritonavir, oseltamivir, azithromycin and meropenem at a regional hospital. He was intubated and transferred to the ICU in the tertiary university hospital on day 10 (ICU day 1). Interferon beta-1b subcutaneous injection was initiated immediately to enhance anti-viral therapy, and favipiravir on ICU day 10 upon availability. Progression of organ dysfunctions necessitated inhalation of nitrogen oxide for respiratory dysfunction, noradrenaline for cardiovascular dysfunction and continuous renal replacement therapy for renal dysfunction. His blood samples PCR also tested positive for SARS-CoV-2, indicating viremia, concomitantly with elevated IL-6 levels. VV-ECMO was initiated after sudden exacerbation of respiratory dysfunction on ICU day 7 to maintain oxygenation. The sustained excessive inflammatory cytokines in the present case might have led to the exacerbation of the disease, requiring vigorous organ support therapies to allow for survival and recovery from the rapid progression of multiple organ dysfunctions and severe respiratory failure.
- Published
- 2020
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