Details of a Researcher - Uwamino, Yoshifumi

Papers - Uwamino, Yoshifumi

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The effect of the E484K mutation of SARS-CoV-2 on the neutralizing activity of antibodies from BNT162b2 vaccinated individuals.

Uwamino Y, Yokoyama T, Shimura T, Nishimura T, Sato Y, Wakui M, Kosaki K, Hasegawa N, Murata M

Vaccine 40 ( 13 ) 1928 - 1931 2022.03

ISSN 0264-410X

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The effect of the E484K mutation of SARS-CoV-2 on the neutralizing activity of antibodies from BNT162b2 vaccinated individuals.

Yoshifumi Uwamino, Takashi Yokoyama, Takako Shimura, Tomoyasu Nishimura, Yasunori Sato, Masatoshi Wakui, Kenjiro Kosaki, Naoki Hasegawa, Mitsuru Murata

Vaccine 40 ( 13 ) 1928 - 1931 2022.03

The reduced vaccine efficacy against the SARS-CoV-2 variant lineage B. 1.351 (beta variant) containing the E484K and N501Y mutations is well known. The E484K mutation in SARS-CoV-2 is thought to be responsible for weakened humoral immunity. Vaccine efficacy against the R.1 lineage, which contains the E484K mutation but not the N501Y mutation, is uncertain. Serum samples were collected from 100 healthy Japanese participants three weeks after receiving the second dose of the BNT162b2 vaccine, and serum neutralization antibody titers were measured against five SARS-CoV-2 variants. The geometric mean neutralization titers measured for the original and R.1 lineages were equivalent (91.90 ± 2.40 and 102.67 ± 2.28, respectively), whereas a low titer was measured for the beta variant (18.03 ± 1.92). Although further investigations with other variant strains and serum samples are essential, our results imply that the weakened humoral response is not caused solely by the E484K mutation. (UMIN000043340).

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医療従事者における新型コロナウイルスの感染状況調査

西村知泰, 森正明, 長谷川直樹, 上蓑義典, 宇野俊介

大和証券ヘルス財団研究業績集 ((公財)大和証券ヘルス財団) ( 45 ) 32 - 35 2022.03

医療従事者におけるCOVID-19の適切な感染対策を検討するため、血清抗体検査の陽性率から感染状況を推測した。さらに、血清抗体陽性者と陰性者の背景や臨床情報を比較し、感染者の特徴や感染危険因子を探索した。本大学医学部と大学病院に所属する医療従事者に対して2020年8月に実施した定期検査の際に、研究参加同意の得られた2341人を対象とした。COVID-19の既往歴のある21人を除外した2320人におけるIgG抗体陽性者は20人(0.862%)であった。年齢や職種では抗体陽性率に有意差はなかったが、性別は男性の方が有意に抗体陽性率が高かった。抗体陽性者は何らかの症状、特に嗅覚障害や味覚障害、発熱があった者で多かった。医療機関におけるCOVID-19の集団感染を防ぐために、医療従事者は適切な標準感染予防策と感染予防経路別予防策を実施し、発熱や嗅覚・味覚障害といった症状が出現した際は速やかに就業を中止すべきであると考えられた。

The effect of the E484K mutation of SARS-CoV-2 on the neutralizing activity of antibodies from BNT162b2 vaccinated individuals

Yoshifumi Uwamino, Takashi Yokoyama, Takako Shimura, Tomoyasu Nishimura, Yasunori Sato, Masatoshi Wakui, Kenjiro Kosaki, Naoki Hasegawa, Mitsuru Murata

VACCINE (ELSEVIER SCI LTD) 40 ( 13 ) 1928 - 1931 2022.03

ISSN 0264-410X

The reduced vaccine efficacy against the SARS-CoV-2 variant lineage B. 1.351 (beta variant) containing the E484K and N501Y mutations is well known. The E484K mutation in SARS-CoV-2 is thought to be responsible for weakened humoral immunity. Vaccine efficacy against the R.1 lineage, which contains the E484K mutation but not the N501Y mutation, is uncertain. Serum samples were collected from 100 healthy Japanese participants three weeks after receiving the second dose of the BNT162b2 vaccine, and serum neutralization antibody titers were measured against five SARS-CoV-2 variants. The geometric mean neutralization titers measured for the original and R.1 lineages were equivalent (91.90 +/- 2.40 and 102.67 +/- 2. 28, respectively), whereas a low titer was measured for the beta variant (18.03 +/- 1.92). Although further investigations with other variant strains and serum samples are essential, our results imply that the weakened humoral response is not caused solely by the E484K mutation. (UMIN000043340). (c) 2022 Elsevier Ltd. All rights reserved.

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Young age, female sex, and presence of systemic adverse reactions are associated with high post-vaccination antibody titer after two doses of BNT162b2 mRNA SARS-CoV-2 vaccination: An observational study of 646 Japanese healthcare workers and university staff.

Yoshifumi Uwamino, Toshinobu Kurafuji, Yasunori Sato, Yukari Tomita, Ayako Shibata, Akiko Tanabe, Yoko Yatabe, Masayo Noguchi, Tomoko Arai, Akemi Ohno, Hiromitsu Yokota, Wakako Yamasawa, Shunsuke Uno, Tomoyasu Nishimura, Naoki Hasegawa, Hideyuki Saya, Masatoshi Wakui, Mitsuru Murata

Vaccine (Vaccine) 40 ( 7 ) 1019 - 1025 2022.02

ISSN 0264410X

BACKGROUND: SARS-CoV-2 vaccination has started worldwide, including Japan. Although high rates of vaccine response and adverse reactions of BNT162b2 vaccine have been reported, knowledge about the relationship between sex differences and antibody response is limited. Furthermore, it is uncertain whether adverse reactions are associated with the vaccine response. METHODS: This prospective observational study included 673 Japanese participants working in a medical school and its affiliated hospital in Tokyo, Japan (UMIN000043340). Serum samples were collected before the first dose and three weeks after the second dose of BNT162b2 vaccine, and antibody titers against the receptor-binding domain of the spike protein of SARS-CoV-2 were measured. Answers to questionnaires about background characteristics and adverse reactions were obtained at the time of sample collection, and the relationship between antibody titers was analyzed. RESULTS: After excluding participants who did not complete receiving two doses of vaccination or two series of serum sample collection, 646 participants were analyzed. Although all participants became sero-positive after vaccination, antibody titers were highly variable among individuals (260.9-57,399.7A U/mL), with a median titer of 13478.0AU/mL. Mean titer was higher in females than in males and higher in young (≤45 years old) participants than in aged (>45 years old) participants. Participants who experienced adverse reactions demonstrated a higher antibody titer after vaccination than those without adverse reactions. Multivariable analysis demonstrated that young age, female sex, and adverse reactions after the second dose were independently related to higher antibody titers after the second dose. DISCUSSION: A favorable antibody response was observed after two doses of BNT162b2 vaccination among mostly healthy Japanese participants, especially among female and young participants. Although further investigation is essential, our results imply that the systemic adverse reactions (i.e., fever and general fatigue) are associated with a higher antibody response that indicates the acquisition of humoral immunity.

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Pro108Ser mutation of SARS-CoV-2 3CLpro reduces the enzyme activity and ameliorates the clinical severity of COVID-19.

Kodai Abe, Yasuaki Kabe, Susumu Uchiyama, Yuka W Iwasaki, Hirotsugu Ishizu, Yoshifumi Uwamino, Toshiki Takenouchi, Shunsuke Uno, Makoto Ishii, Takahiro Maruno, Masanori Noda, Mitsuru Murata, Naoki Hasegawa, Hideyuki Saya, Yuko Kitagawa, Koichi Fukunaga, Masayuki Amagai, Haruhiko Siomi, Makoto Suematsu, Kenjiro Kosaki

Scientific reports (Scientific Reports) 12 ( 1 ) 1299 - 1299 2022.01

Recently, an international randomized controlled clinical trial showed that patients with SARS-CoV-2 infection treated orally with the 3-chymotrypsin-like protease (3CLpro) inhibitor PF-07321332 within three days of symptom onset showed an 89% lower risk of COVID-19-related hospital admission/ death from any cause as compared with the patients who received placebo. Lending support to this critically important result of the aforementioned trial, we demonstrated in our study that patients infected with a SARS-Cov-2 sub-lineage (B.1.1.284) carrying the Pro108Ser mutation in 3CLpro tended to have a comparatively milder clinical course (i.e., a smaller proportion of patients required oxygen supplementation during the clinical course) than patients infected with the same sub-lineage of virus not carrying the mutation. Characterization of the mutant 3CLpro revealed that the Kcat/Km of the 3CLpro enzyme containing Ser108 was 58% lower than that of Pro108 3CLpro. Hydrogen/deuterium-exchange mass spectrometry (HDX-MS) revealed that the reduced activity was associated with structural perturbation surrounding the substrate-binding region of the enzyme, which is positioned behind and distant from the 108th amino acid residue. Our findings of the attenuated clinical course of COVID-19 in patients infected with SARS-CoV-2 strains with reduced 3CLpro enzymatic activity greatly endorses the promising result of the aforementioned clinical trial of the 3CLpro inhibitor.

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COVID-19 vaccine induced interstitial lung disease.

Ayumi Yoshifuji, Kota Ishioka, Yuya Masuzawa, Shuntaro Suda, Saori Murata, Yoshifumi Uwamino, Motoko Fujino, Hiromi Miyahara, Naoki Hasegawa, Munekazu Ryuzaki, Haruhiko Hoshino, Kazuhiko Sekine

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy (Journal of Infection and Chemotherapy) 28 ( 1 ) 95 - 98 2022.01

ISSN 1341321X

A 60-year-old man presented with dyspnea four days after the second dose of the coronavirus disease (COVID-19) vaccine. Imaging revealed extensive ground-glass opacification. Blood tests were notable for elevated KL-6 levels. Bronchoalveolar lavage fluid analysis showed increased lymphocyte-dominant inflammatory cells and decreased CD4/CD8 ratio. These findings were consistent with the diagnosis of drug-induced interstitial lung disease (DIILD). To the best of our knowledge, this has never been reported in previous literature. Treatment with glucocorticoids relieved his symptoms. This paper highlights that although extremely rare, COVID-19 vaccine could cause DIILD, and early diagnosis and treatment are crucial to improve patient outcomes.

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Usefulness of the FilmArray Meningitis/Encephalitis Panel in diagnosis of central nervous system infection after allogeneic hematopoietic stem cell transplantation.

Takehiko Mori, Yuya Koda, Jun Kato, Masatoshi Sakurai, Yoshifumi Uwamino, Naoki Hasegawa

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer (Supportive Care in Cancer) 30 ( 1 ) 5 - 8 2022.01

ISSN 09414355

PURPOSE: The BioFire FilmArray® Meningitis/Encephalitis Panel (FAMEP) is designed to rapidly and accurately detect common multiple pathogens that cause central nervous system (CNS) infection, including viruses, bacteria, and yeast. The FAMEP's usefulness in the setting of allogeneic hematopoietic stem cell transplantation (HSCT) has not been fully evaluated. This retrospective study evaluated the usefulness of the FAMEP in the screening for CNS infection after allogeneic HSCT. METHODS: Cerebrospinal fluid (CSF) was obtained from 12 patients to evaluate the causes of CNS disorders after allogeneic HSCT, and the FAMEP was applied. RESULTS: The median day of the FAMEP evaluations was 27 days post-transplant (range, 0-390). Human herpesvirus 6 (HHV-6) was detected in three patients and cytomegalovirus was detected in one patient, leading to the diagnosis of encephalitis/myelitis. In three patients (HHV-6, n = 2; CMV, n = 1), the presence of the viruses was confirmed by conventional real-time polymerase chain reaction (PCR). However, in the remaining patient with HHV-6 detected by the AMEP, HHV-6 was not detected by real-time PCR at the onset but was detected 7 days later. The treatments for the detected viruses improved the clinical conditions in the four patients. CONCLUSIONS: Our results suggest that the FAMEP can be a useful sensitive assay in the screening and diagnosis of CNS viral infections after allogeneic HSCT.

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Mycobacterium abscessus complexに対するNacubactamとβラクタム薬の併用効果

三澤可奈, 西村知泰, 榎木裕紀, 田口和明, 宇野俊介, 上蓑義典, 松元一明, 長谷川直樹

日本化学療法学会雑誌 ((公社)日本化学療法学会) 70 ( 1 ) 162 - 163 2022.01

ISSN 1340-7007

Impact of rifampicin on the pharmacokinetics of clarithromycin and 14-hydroxy clarithromycin in patients with multidrug combination therapy for pulmonary Mycobacterium avium complex infection.

Osamu Iketani, Akari Komeya, Yuki Enoki, Kazuaki Taguchi, Shunsuke Uno, Yoshifumi Uwamino, Kazuaki Matsumoto, Junko Kizu, Naoki Hasegawa

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy (Journal of Infection and Chemotherapy) 28 ( 1 ) 61 - 66 2022.01

ISSN 1341321X

INTRODUCTION: Clarithromycin (CAM), ethambutol (EB), and rifampicin (RFP) combination therapy is used to treat pulmonary Mycobacterium avium complex (MAC) infection; however, serum CAM concentration decreases due to RFP-mediated induction of CYP3A activity. Therefore, we investigated the pharmacokinetics of CAM, 14-hydroxy clarithromycin (14-OH CAM), EB, and RFP in patients receiving this three-drug combination therapy. METHODS: CAM monotherapy was started, EB was added 2 weeks later, and RFP was added 2 weeks after that. Serum CAM, 14-OH CAM, EB, and RFP concentrations were measured before and at 2, 4, 6, and 12 or 24 h after administration on days 14, 28, and 42, and pharmacokinetic parameters were calculated. RESULTS: Median area under the curve (AUC) of CAM decreased by 92.1% from 0 to 12 h after concomitant administration of RFP compared with CAM monotherapy [1.7 (interquartile range [IQR], 1.4-1.8) μg·h/mL vs. 21.5 (IQR, 17.7-32.3) μg·h/mL, respectively]. In contrast, median AUC of 14-OH CAM was not significantly different between concomitant administration of RFP [9.1 (IQR, 7.9-10.9) μg·h/mL] and CAM monotherapy [8.2 (IQR, 6.3-9.3) μg·h/mL]. AUCs of CAM and 14-OH CAM did not change in CAM+EB combination therapy. CONCLUSIONS: When RFP is combined with CAM in the treatment of pulmonary MAC infection, the blood concentration of CAM significantly decreased and that of the active metabolite 14-OH CAM increased, but not significantly. Our results suggest that combination therapy with CAM and RFP needs to be reconsidered and may require dose modification in the treatment of pulmonary MAC infection.

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Efficient automated semi-quantitative urine culture analysis via BD Urine Culture App.

Yoshifumi Uwamino, Mika Nagata, Wataru Aoki, Ai Kato, Miho Daigo, Osamu Ishihara, Hirotaka Igari, Rika Inose, Naoki Hasegawa, Mitsuru Murata

Diagnostic microbiology and infectious disease (Diagnostic Microbiology and Infectious Disease) 102 ( 1 ) 115567 - 115567 2022.01

ISSN 07328893

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Mapping the human genetic architecture of COVID-19

Niemi M.E.K., Karjalainen J., Liao R.G., Neale B.M., Daly M., Ganna A., Pathak G.A., Andrews S.J., Kanai M., Veerapen K., Fernandez-Cadenas I., Schulte E.C., Striano P., Marttila M., Minica C., Marouli E., Karim M.A., Wendt F.R., Savage J., Sloofman L., Butler-Laporte G., Kim H.N., Kanoni S., Okada Y., Byun J., Han Y., Uddin M.J., Smith G.D., Willer C.J., Buxbaum J.D., Mehtonen J., Finucane H., Cordioli M., Martin A.R., Zhou W., Pasaniuc B., Julienne H., Aschard H., Shi H., Yengo L., Polimanti R., Ghoussaini M., Schwartzentruber J., Dunham I., Chwialkowska K., Francescatto M., Trankiem A., Balaconis M.K., Davis L., Lee S., Priest J., Renieri A., Sankaran V.G., van Heel D., Deelen P., Brent Richards J., Nakanishi T., Biesecker L., Eric Kerchberger V., Kenneth Baillie J., Mari F., Bernasconi A., Ceri S., Canakoglu A., Wolford B., Faucon A., Dutta A.K., Schurmann C., Harry E., Birney E., Nguyen H., Nasir J., Kaunisto M., Solomonson M., Dueker N., Vadgama N., Limou S., Rahmouni S., Mbarek H., Darwish D., Uddin M.M., Albertos R., Pérez-Tur J., Li R., Folkersen L., Moltke I., Koelling N., Teumer A., Kousathanas A., Utrilla A., Verdugo R.A., Zárate R., Medina-Gómez C., Gómez-Cabrero D., Carnero-Montoro E., Cadilla C.L., Moreno-Estrada A., Garmendia A., Moya L., Sedaghati-Khayat B.

Nature (Nature) 600 ( 7889 ) 472 - 477 2021.12

ISSN 00280836

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

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Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians.

Yuko Sato, Koji Atarashi, Damian R Plichta, Yasumichi Arai, Satoshi Sasajima, Sean M Kearney, Wataru Suda, Kozue Takeshita, Takahiro Sasaki, Shoki Okamoto, Ashwin N Skelly, Yuki Okamura, Hera Vlamakis, Youxian Li, Takeshi Tanoue, Hajime Takei, Hiroshi Nittono, Seiko Narushima, Junichiro Irie, Hiroshi Itoh, Kyoji Moriya, Yuki Sugiura, Makoto Suematsu, Nobuko Moritoki, Shinsuke Shibata, Dan R Littman, Michael A Fischbach, Yoshifumi Uwamino, Takashi Inoue, Akira Honda, Masahira Hattori, Tsuyoshi Murai, Ramnik J Xavier, Nobuyoshi Hirose, Kenya Honda

Nature (Nature) 599 ( 7885 ) 458 - 464 2021.11

ISSN 00280836

Centenarians have a decreased susceptibility to ageing-associated illnesses, chronic inflammation and infectious diseases1-3. Here we show that centenarians have a distinct gut microbiome that is enriched in microorganisms that are capable of generating unique secondary bile acids, including various isoforms of lithocholic acid (LCA): iso-, 3-oxo-, allo-, 3-oxoallo- and isoallolithocholic acid. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from the faecal microbiota of a centenarian, we identified Odoribacteraceae strains as effective producers of isoalloLCA both in vitro and in vivo. Furthermore, we found that the enzymes 5α-reductase (5AR) and 3β-hydroxysteroid dehydrogenase (3β-HSDH) were responsible for the production of isoalloLCA. IsoalloLCA exerted potent antimicrobial effects against Gram-positive (but not Gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and Enterococcus faecium. These findings suggest that the metabolism of specific bile acids may be involved in reducing the risk of infection with pathobionts, thereby potentially contributing to the maintenance of intestinal homeostasis.

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Virucidal Effect of the Mesoscopic Structure of CAC-717 on Severe Acute Respiratory Syndrome Coronavirus-2.

Takashi Yokoyama, Tomoyasu Nishimura, Yoshifumi Uwamino, Kenjiro Kosaki, Koichi Furusaki, Rumiko Onishi, Takashi Onodera, Makoto Haritani, Katsuaki Sugiura, Rikio Kirisawa, Naoki Hasegawa

Microorganisms (Microorganisms) 9 ( 10 ) 2021.10

ISSN 2076-2607

Here, the virucidal effect of calcium bicarbonate with a mesoscopic structure (CAC-717) on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was determined. Assays showed that CAC-717 had a strong virucidal effect on all examined SARS-CoV-2 isolates, including variant strains. The viral infectivity decreased within 15 s, and the virucidal activity of CAC-717 at a 1:49 ratio was similar to that of ethanol disinfectant. CAC-717 neutralization eliminated this virucidal effect, indicating that the alkaline condition of CAC-717 is important for virus inactivation and is an indicator of its mesoscopic structure and virucidal activity. The virucidal effect was observed in the presence of organic matter (bovine serum albumin). CAC-717 is a non-invasive and non-flammable substance with a low environmental burden, and its usefulness as a novel disinfectant has been confirmed.

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SARS-CoV-2 Infection among Medical Institution Faculty and Healthcare Workers in Tokyo, Japan.

Tomoyasu Nishimura, Yoshifumi Uwamino, Shunsuke Uno, Shoko Kashimura, Toshikimi Shiraki, Toshinobu Kurafuji, Maasa Morita, Masayo Noguchi, Tatsuhiko Azegami, Nobuko Yamada-Goto, Ayano Murai-Takeda, Hirokazu Yokoyama, Kazuyo Kuwabara, Suzuka Kato, Minako Matsumoto, Aya Hirata, Miho Iida, Sei Harada, Tamami Ishizaka, Kana Misawa, Mitsuru Murata, Hideyuki Saya, Masayuki Amagai, Yuko Kitagawa, Tsutomu Takeuchi, Masaaki Mori, Toru Takebayashi, Naoki Hasegawa

Internal medicine (Tokyo, Japan) (Internal Medicine) 60 ( 16 ) 2569 - 2575 2021.08

ISSN 09182918

Objective To consider effective measures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in medical institutions, this study estimated the SARS-CoV-2 infection rate among healthcare workers (HCWs) in Tokyo, Japan, and determined the specific findings for mild coronavirus disease 2019 (COVID-19) cases. Methods This study analyzed the results of serologic tests to detect immunoglobulin G antibodies against SARS-CoV-2 and evaluated the demographic and clinical characteristics of the faculty and HCWs at a Tokyo medical institution in August 2020. The demographic and clinical characteristics of participants with antibody-positive results were compared to those of participants with antibody-negative results. Materials This study recruited 2,341 faculty and HCWs at a Tokyo medical institution, 21 of whom had a COVID-19 history. Results Of the 2,320 participants without a COVID-19 history, 20 (0.862%) had positive serologic test results. A fever and dysgeusia or dysosmia occurred with greater frequency among the participants with positive test results than in those with negative results [odds ratio (OR), 5.475; 95% confidence interval (CI), 1.960-15.293 and OR, 24.158; 95% CI, 2.693-216.720, respectively]. No significant difference was observed in the positivity rate between HCWs providing medical care for COVID-19 patients using adequate protection and other HCWs (OR, 2.514; 95% CI, 0.959-6.588). Conclusion To reduce the risk of COVID-19 spread in medical institutions, faculty and HCWs should follow standard and necessary transmission-based precautions, and those with a fever and dysgeusia or dysosmia should excuse themselves from work as soon as possible.

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Rheumatoid arthritis with nontuberculous mycobacterial pulmonary disease: a retrospective, single-centre cohort study.

Hiroshi Takei, Naoshi Nishina, H O Namkoong, Katsuya Suzuki, Yoshifumi Uwamino, Naoki Hasegawa, Tsutomu Takeuchi

Modern rheumatology (Modern Rheumatology) 32 ( 3 ) 534 - 540 2021.08

ISSN 14397595

OBJECTIVES: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a rare but important comorbidity of rheumatoid arthritis (RA). Our objective was to investigate the association between NTM-PD and RA, especially regarding the immunosuppressive treatment of RA such as biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: We conducted a retrospective, single-centre cohort study. All RA patients regularly followed up at our rheumatology division in December 2012 were included in the study, and followed for 5 years. RESULTS: At baseline, 26 of 1639 RA patients had NTM-PD. During the observation period, 14 were newly diagnosed with NTM-PD. For new diagnosis of NTM-PD, bDMARD use at baseline was not a significant risk factor. Among the 40 patients with NTM-PD, 16 were treated with a total of 27 bDMARDs after NTM-PD diagnosis. They did not present with a greater exacerbation of NTM-PD than those not treated with bDMARDs (25 vs. 17%, p = .52). A total of 55 patients died, but nobody died of NTM-PD. NTM-PD was not associated with worse mortality in multivariate analysis (hazard ratio, 2.0; 95% CI, 0.6-6.4; p = .26). CONCLUSIONS: Biological DMARD was not associated with worse prognosis of NTM-PD. Careful use of bDMARDs could be tolerated in RA patients with NTM-PD.

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Meningitis caused by Listeria monocytogenes in a locally advanced cervical cancer patient with pyometra: A case report.

Yusuke Matoba, Hiroshi Nishio, Koji Sekiguchi, Shunsuke Uno, Kenta Masuda, Makiko Hiramatsu, Mio Takahashi, Maki Oishi, Yoshifumi Uwamino, Sho Uchida, Yugaku Daté, Tohru Morisada, Kouji Banno, Jin Nakahara, Daisuke Aoki

Gynecologic oncology reports (Gynecologic Oncology Reports) 37 100799 - 100799 2021.08

ISSN 2352-5789

Locally advanced cervical cancer occasionally induces pyometra, but there have been no reports of meningitis where pyometra is the cause of infection. Here, we report a case of Listeria monocytogenes meningitis related to pyometra during concurrent chemoradiotherapy (CCRT) in a cervical cancer patient. The patient, a 77-year-old woman, was diagnosed with Stage IIB (FIGO 2018) cervical adenocarcinoma, and CCRT was initiated. Pyometra was exacerbated during CCRT, and after her first brachytherapy, she presented at our hospital with fever and decreased consciousness level. After admission to the Intensive Care Unit, the patient lost consciousness and experienced frequent seizures; tracheal intubation was required. Whole-body computed tomography revealed pyometra; therefore, transvaginal removal of the abscess was performed. Laboratory tests and vital signs indicated septic shock, and meropenem was administered. L. monocytogenes was detected in the abscess from the uterine cavity and the blood cultures on the third day of hospitalization. A lumbar puncture was performed on the same day to investigate whether the patient had meningitis. A FilmArray meningitis/encephalitis panel test of the spinal fluid revealed L. monocytogenes. After the diagnosis of meningitis with L. monocytogenes, ampicillin and gentamicin were started, and the blood test results gradually improved. Five months after the initial episode, her consciousness recovered, however she still received mechanical ventilatory support. L. monocytogenes infections can occur in patients undergoing chemotherapy, even without the use of steroids or immunosuppressive agents. In cases with pyometra, intrauterine manipulation can increase the risk of severe infection.

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Three cases of otitis media caused by Mycobacterium abscessus subsp. abscessus: Importance of medical treatment and efficacy of surgery.

Yuri Nishiyama, Takanori Nishiyama, Sho Kanzaki, Naoki Oishi, Masato Fujioka, Hiroyuki Yamada, Chihiro Ebisuno, Mayumi Kaiho, Yoshifumi Uwamino, Hanako Fukano, Yoshihiko Hoshino, Naoki Hasegawa, Kaoru Ogawa

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy (Journal of Infection and Chemotherapy) 27 ( 8 ) 1251 - 1257 2021.08

ISSN 1341321X

This study aimed to assess the clinical presentation, antibiotic therapy, surgery, and outcomes in patients with otitis media caused by Mycobacterium abscessus subsp. abscessus and discuss the efficacy of surgery. This is a retrospective case review of three patients diagnosed with otomastoiditis caused by M. abscessus subsp. abscessus. All patients had refractory otorrhea. One patient had granulation tissue in the tympanic membrane. They received medical treatment and underwent surgery. Otorrhea was resolved several months after the initiation of long-term multiantibiotic therapy in all cases. The timing of surgery varied among patients. Before initiating antibiotic therapy, mastoidectomy was performed to achieve definitive diagnosis in two patients, and wound dehiscence developed in these patients. Two patients underwent debridement after the initiation of multiantibiotic therapy. After antibiotic administration, tympanoplasty was performed to improve hearing in one patient. All patients achieved culture negativity after treatment, and no recurrences have been noted. From three cases, it is suggested that the mainstay of treatment for M. abscessus subsp. abscessus is long-term multiantibiotic therapy, and surgery itself may have little effect on achieving ear dryness. Thus, in most patients, drug therapy should be prioritized. Considering postoperative complications, surgery before achieving ear dryness should be avoided, except in emergency cases. In addition, if the diagnosis is not confirmed by repeated bacteriological tests, mastoidectomy should be performed to collect specimens. Tympanoplasty for hearing loss or eardrum perforation is recommended after discontinuation of medications.

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Universal Polymerase Chain Reaction Screening for Severe Acute Respiratory Syndrome Coronavirus 2 in Asymptomatic Patients Before Hospital Admission in Tokyo, Japan.

Sho Uchida, Yoshifumi Uwamino, Shunsuke Uno, Mika Nagata, Wataru Aoki, Mitsuru Murata, Yuko Kitagawa, Naoki Hasegawa

Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology (Journal of Clinical Virology) 142 104915 - 104915 2021.07

ISSN 13866532

OBJECTIVES: Universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; i.e., the causative agent of coronavirus disease 2019 [COVID-19]) polymerase chain reaction (PCR) screening before admission has been adopted by several hospitals to prevent nosocomial SARS-CoV-2 transmission from asymptomatic and pre-symptomatic patients. However, screening usefulness remains unclear because it depends on the regional COVID-19 prevalence, and only a few large-scale studies have been reported. Here we describe the universal PCR screening performed in our hospital before admission of more than 12,000 patients and their attendants to evaluate the usefulness of the screening. METHODS: We retrospectively described the universal PCR screening results for asymptomatic patients and their attendants before planned admissions at a hospital in Tokyo, Japan, from August 3, 2020, through March 31, 2021. Nasopharyngeal swab samples were collected at an in-hospital PCR center. RESULTS: In total, 12,133 persons (11,859 asymptomatic patients and 274 attendants) underwent PCR screening; nine (0.07%) tested positive for SARS-CoV-2 RNA. CONCLUSIONS: Universal PCR screening may be useful for the advanced detection of SARS-CoV-2 infected patients with or without symptoms, which can be a potential source of nosocomial SARS-CoV-2 transmission.

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Accuracy of rapid antigen detection test for nasopharyngeal swab specimens and saliva samples in comparison with RT-PCR and viral culture for SARS-CoV-2 detection.

Yoshifumi Uwamino, Mika Nagata, Wataru Aoki, Terumichi Nakagawa, Rika Inose, Hiromitsu Yokota, Yuri Furusawa, Yuko Sakai-Tagawa, Kiyoko Iwatsuki-Horimoto, Yoshihiro Kawaoka, Naoki Hasegawa, Mitsuru Murata

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy (Journal of Infection and Chemotherapy) 27 ( 7 ) 1058 - 1062 2021.07

ISSN 1341321X

INTRODUCTION: Rapid antigen detection (RAD) tests are convenient tools for detecting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in clinics, and testing using saliva samples could decrease the risk of infection during sample collection. This study aimed to assess the accuracy of the SARS-CoV-2 RAD for testing of nasopharyngeal swab specimens and saliva samples in comparison with the RT-PCR tests and viral culture for detecting viable virus. METHODS: One hundred seventeen nasopharyngeal swab specimens and 73 saliva samples with positive results on RT-PCR were used. Residual samples were assayed using a commercially available RAD test immediately, and its positivity was determined at various time points during the clinical course. The concordance between 54 nasopharyngeal swab samples and saliva samples that were collected simultaneously was determined. Viral culture was performed on 117 samples and compared with the results of the RAD test. RESULTS: The positive rate of RAD test using saliva samples was low throughout the clinical course. Poor concordance was observed between nasopharyngeal swab specimens and saliva samples (75.9%, kappa coefficient 0.310). However, a substantially high concordance between the RAD test and viral culture was observed in both nasopharyngeal swab specimens (86.8%, kappa coefficient 0.680) and saliva samples (95.1%, kappa coefficient 0.643). CONCLUSIONS: The sensitivity of the SARS-CoV-2 RAD test was insufficient, particularly for saliva samples. However, a substantially high concordance with viral culture suggests its potential utility as an auxiliary test for estimating SARS-CoV-2 viability.

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