Details of a Researcher - TAKAHASHI Satoshi

Papers - TAKAHASHI Satoshi

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Nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis from male urethritis in Japan: Comparison with the first surveillance report.

Satoshi Takahashi, Mitsuru Yasuda, Koichiro Wada, Masahiro Matsumoto, Hiroshi Hayami, Kanao Kobayashi, Jun Miyazaki, Hiroshi Kiyota, Tetsuya Matsumoto, Hiroshi Yotsuyanagi, Kazuhiro Tateda, Junko Sato, Hideaki Hanaki, Naoya Masumori, Yoshiki Hiyama, Shin Egawa, Hiroki Yamada, Kazumasa Matsumoto, Kiyohito Ishikawa, Shingo Yamamoto, Yoshikazu Togo, Kazushi Tanaka, Katsumi Shigemura, Shinya Uehara, Hiroyuki Kitano, Keijiro Kiyoshima, Ryoichi Hamasuna, Kenji Ito, Hideo Hirayama, Shuichi Kawai, Yutaka Shiono, Takahiro Maruyama, Shin Ito, Mutsumasa Yoh, Masayasu Ito, Koichi Hatano, Hideari Ihara, Satoshi Uno, Koichi Monden, Teruhiko Yokoyama, Kazuo Takayama, Toru Sumii, Hitoshi Kadena, Motoshi Kawahara, Takahide Hosobe, Masanobu Izumitani, Motonori Kano, Hirofumi Nishimura, Ryuji Fujita, Shinichi Kaji, Kenji Hayashi, Takanori Tojo, Masaru Matumura

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 28 ( 1 ) 1 - 5 2022.01 [International journal]

The Urogenital Sub-committee and the Surveillance Committee of the Japanese Society of Chemotherapy, The Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology conducted the second nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis. In this second surveillance study, clinical urethral discharge specimens were collected from patients with urethritis in 26 hospitals and clinics from May 2016 to July 2017. Based on serial cultures, the minimum inhibitory concentration (MIC) could be determined for 41 isolates; the MICs (MIC90) of ciprofloxacin, levofloxacin, tosufloxacin, sitafloxacin, doxycycline, minocycline, erythromycin, clarithromycin, azithromycin and solithromycin were 2 μg/ml (2 μg/ml), 1 μg/ml (0.5 μg/ml), 0.25 μg/ml (0.25 μg/ml), 0.125 μg/ml (0.063 μg/ml), 0.125 μg/ml (0.125 μg/ml), 0.25 μg/ml (0.25 μg/ml), 0.031 μg/ml (0.031 μg/ml), 0.25 μg/ml (0.125 μg/ml), and 0.016 μg/ml (0.008 μg/ml), respectively. In summary, this surveillance project did not identify any strains resistant to fluoroquinolone, tetracycline, or macrolide agents in Japan. In addition, the MIC of solithromycin was favorable and lower than that of other antimicrobial agents. However, the MIC of azithromycin had a slightly higher value than that reported in the first surveillance report, though this might be within the acceptable margin of error. Therefore, the susceptibility of azithromycin, especially, should be monitored henceforth.

Impaired tryptophan metabolism in the gastrointestinal tract of patients with critical coronavirus disease 2019.

Yoshihiro Yokoyama, Tomoko Ichiki, Tsukasa Yamakawa, Yoshihisa Tsuji, Koji Kuronuma, Satoshi Takahashi, Eichi Narimatsu, Hiroshi Nakase

Frontiers in medicine 9 941422 - 941422 2022 [International journal]

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is still causing a global pandemic. But the mechanism of COVID-19 severity is not well elucidated. MATERIALS AND METHODS: We conducted two single-center observational studies of patients with COVID-19. In the first study, the enrolled patients were distinguished based on critical vs. non-critical COVID-19. We collected blood samples from the patients at admission to measure markers related to inflammation and thrombosis and stool samples to analyze the fecal microbiome, metabolome, and calprotectin level. In the second study, we collected ileum and colon tissue samples from patients with critical COVID-19 who required colonoscopy due to severe gastrointestinal symptoms and analyzed mucosal gene expression. RESULTS: A total of 19 blood samples and 10 stool samples were collected. Interleukin (IL)-6 was the only serum inflammatory marker with significantly higher levels in the critical group than in the non-critical group. The fecal calprotectin level in the critical group was significantly higher than that in the non-critical group (P = 0.03), regardless of the presence of gastrointestinal symptoms. Stool metabolomic analysis showed that the level of indole-3-propionic acid, a ligand for aryl hydrocarbon receptor (AhR), was markedly decreased in the critical group compared to that in the non-critical group (P = 0.01). The expression of genes involved in tryptophan metabolism, including ACE2, AHR, CARD9, and IL22, was downregulated in the ileum of critical COVID-19 patients who required a colonoscopy. DISCUSSION: Critical COVID-19 patients have gastrointestinal inflammation potentially caused by impaired tryptophan metabolism in the small intestine due to decreased expression of genes involved in tryptophan metabolism.

Self-reported Smell and Taste Disorders in Patients With COVID-19: A Japanese Single-center Study.

Keisuke Yamamoto, Yoshihiro Fujiya, Koji Kuronuma, Noriko Ogasawara, Tsuyoshi Ohkuni, Shin-Ichi Yokota, Satoshi Takahashi, Kenichi Takano

In vivo (Athens, Greece) 36 ( 2 ) 918 - 924 2022 [International journal]

BACKGROUND/AIM: Smell and taste disorders are among the most common symptoms of COVID-19. However, the relationship between smell and taste disorders and systemic symptoms is not fully understood in Japan. PATIENTS AND METHODS: Questionnaires were mailed to 105 of 111 COVID-19 patients who were hospitalized at our hospital between March and July 2020 in Japan. RESULTS: A total of 74 patients (response rate: 70.5%) completed the survey. Of these, six patients (8.1%) presented with smell disorders only, 16 (21.6%) presented with taste disorders only, and 17 (23.0%) presented with both smell and taste disorders. The mean Visual Analog Scale for smell and taste was 0.5 and 20, respectively, at the time of the most severe symptoms. CONCLUSION: Among COVID-19 patients in Japan, smell and taste disorders are often followed by fever and may not be the first symptoms. Sense of smell is particularly impaired. These symptoms often improve, although they sometimes persist for a long time as sequelae.

Guidelines for Infection Control in the Urological Field, including Urinary Tract Management (revised second edition).

Satoshi Takahashi, Soichi Arakawa, Kiyohito Ishikawa, Jun Kamei, Kanao Kobayashi, Katsumi Shigemura, Satoru Takahashi, Yoshiki Hiyama, Ryoichi Hamasuna, Hiroshi Hayami, Satoshi Yazawa, Mitsuru Yasuda, Yoshikazu Togo, Shingo Yamamoto, Koichiro Wada, Toyohiko Watanabe

International journal of urology : official journal of the Japanese Urological Association 28 ( 12 ) 1198 - 1211 2021.12 [International journal]

The Committee for the Development of Guidelines for Infection Control in the Urological Field, including Urinary Tract Management of the Japanese Urological Association, together with its systematic review team and external reviewers, have prepared a set of practice guidelines, an abridged version of which is published herein. These guidelines cover the following topics: (i) foundations of infection control, standard precautions, route-specific precautions, and occupational infection control (including vaccines); (ii) the relationship between urologists and infection control; (iii) infection control in urological wards and outpatient clinics; (iv) response to hepatitis B virus reactivation; (v) infection control in urological procedures and examinations; (vi) prevention of infections occurring in conjunction with medical procedures and examinations; (vii) responses to urinary tract tuberculosis and bacillus Calmette-Guérin; (viii) aseptic handling, cleaning, disinfection, and sterilization of urinary tract endoscopes (principles of endoscope manipulation, endoscope lumen cleaning, and disinfection); (ix) infection control in the operating room (principles of hand washing, preoperative rubbing methods, etc.); (x) prevention of needlestick and blood/bodily fluid exposure and response to accidental exposure; (xi) urinary catheter-associated urinary tract infection and purple urinary bag syndrome; and (xii) urinary catheter-associated urinary tract infections in conjunction with home care. In addressing these topics, the relevant medical literature was searched to the extent possible, and content was prepared for the purpose of providing useful information for clinical practice.

Prognostic value of 6-min walk stress echocardiography in patients with interstitial lung disease.

Kenji Yasui, Satoshi Yuda, Kiyoshi Abe, Kouichi Asanuma, Nozomi Yanagihara, Yuta Sudo, Kimiyuki Ikeda, Atsuko Muranaka, Mitsuo Otsuka, Daigo Nagahara, Hirofumi Ohnishi, Hiroki Takahashi, Tetsuji Miura, Satoshi Takahashi

Journal of echocardiography 19 ( 4 ) 232 - 242 2021.12 [Domestic journal]

BACKGROUND: The 6-min walk test (6MWT) provides prognostic information for patients with interstitial lung disease (ILD). Parameter determined by Doppler echocardiography after the 6MWT (6 MW stress echocardiography) is shown to be a predictor of future development of pulmonary hypertension in patients with connective tissue disease. However, the clinical utility of 6 MW stress echocardiography in predicting cardiopulmonary events in patients with ILD remains unknown. We examined whether parameters determined by 6 MW stress echocardiography independent predictors of adverse events in patients with ILD. METHODS: Echocardiographic examinations were performed in 68 consecutively enrolled patients with ILD (age, 65 ± 10 years, 65% men). A pressure gradient of tricuspid regurgitation (TRPG) and pulmonary vascular resistance (PVRecho) calculated using the following formula [PVRecho = (peak velocity of TR × 10/time-velocity integral of right ventricular outflow (RVOT-VTI)) + 0.16] were measured at baseline and at post 6MWT. Data for parameters of pulmonary functional tests and for 6MWT were collected. RESULTS: During a mean follow-up period of 22 ± 12 months, 22 patients experienced cardiopulmonary events. In univariate analysis, %VC, TRPG, PVRecho, TRPG post 6MWT, and PVRecho post 6MWT were significantly associated with cardiopulmonary events. Multivariate analysis using the Cox proportional hazards model indicated that %VC [hazard ratio (HR): 0.97, p = 0.009] and PVRecho post 6MWT (HR: 1.77, p = 0.004) were independent predictors of cardiopulmonary events in patients with ILD. CONCLUSIONS: In addition to parameters of pulmonary function tests, increased PVRecho post 6MWT is a significant predictor of cardiopulmonary events in patients with ILD. A 6 MW stress echocardiography is useful in assessing the risk of adverse events in patients with ILD.

Clinical performance and potential of a SARS-CoV-2 detection kit without RNA purification steps

Yuki Sato, Takashi Kondo, Mikako Moriai, Shinya Nirasawa, Masachika Saeki, Yuki Yakuwa, Yuki Katayama, Ikumi Kitayama, Ryo Kobayashi, Akemi Endoh, Koichi Asanuma, Yoshihiro Fujiya, Satoshi Takahashi

Journal of Laboratory Medicine ( Walter de Gruyter GmbH ) 45 ( 4-5 ) 205 - 212 2021.10

Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is rapidly spreading globally. Early diagnosis plays an essential role in controlling the infection. Therefore, early and accurate SARS-CoV-2 detection assays along with easy operation are required. The aim of this study was to compare the clinical performance of the Ampdirect™ 2019-nCoV Detection Kit (SHIMADZU assay), which does not require RNA purification steps, with that of the preexisting SARS-CoV-2 detection assays, which use a purified RNA template. Methods: A total of 71 samples (65 nasopharyngeal specimens and 6 sputum specimens) were collected from 32 individuals, including patients infected with SARS-CoV-2 and those with suspected infection. The sensitivity and kappa (κ) coefficient were assessed between the SARS-CoV-2 detection assays using the reference standard, which was defined as a true positive result by any one of the four SARS-CoV-2 detection assays. Results: The overall sensitivity and κ coefficient of the SHIMADZU assay were 86.0% (95% confidence interval [CI]: 77.9-94.2) and 0.83 (95% CI: 0.69-0.96), respectively. In particular, among the 18 samples collected within 10 days from symptom onset, the sensitivity and κ coefficient of the SHIMADZU assay were 100% and 1.0, respectively. Conclusions: Although a relatively small number of samples was evaluated, the SHIMADZU assay showed good analytical performance and as such would be highly useful for the detection of SARS-CoV-2. The test can be performed easily and quickly and has the potential for future applications in situations where a highly sensitive diagnosis is required.

Determination of reactivation rate and risk factors for Hepatitis B virus reactivation in low-positive cases: A retrospective cohort study.

Hitoshi Yonezawa, Shingo Tanaka, Momoko Furuya, Koji Yamada, Koichi Asanuma, Yoshihiro Fujiya, Koji Miyanishi, Satoshi Takahashi, Junji Kato

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 10 ) 1454 - 1458 2021.10 [International journal]

INTRODUCTION: In quantitative assays for hepatitis B virus (HBV) DNA, although the amplification reaction signal is detected for low-positive cases, quantification remains challenging. HBV reactivation has been reported in many studies, but only a few have focused on HBV low-positive cases. This study aimed to determine the reactivation rate and risk factors for HBV reactivation in low-positive cases. METHODS: In this retrospective cohort study, we analyzed 7498 patients who had their HBV DNA measured at Sapporo Medical University Hospital between April 2008 and November 2020. Patient selection criteria were defined as follows: hepatitis B surface antigen was negative; HBV DNA was detectable but not quantifiable at least once. HBV DNA was monitored according to the guidelines for HBV reactivation. RESULTS: In total, 49,086 HBV DNA quantitative tests were performed. HBV DNA levels of 2578 tests were detectable but not quantifiable. Eighty patients met the criteria in this study. The median observation period was 497 days, and the 2-year reactivation rate was 15%. Ten patients had low HBV DNA positivity at baseline. Malignant lymphoma was observed in 15 patients; chemotherapy was used to treat other solid tumors in 35 patients, and immunosuppressive therapy was used in 30 patients. Multivariate analysis revealed that HBV DNA detected below the quantification level at baseline was an independent risk factor for HBV reactivation (adjusted hazard ratio 5.82; P = 0.010). CONCLUSIONS: Patients with low HBV DNA positivity, especially at baseline, are at high risk for HBV reactivation and therefore require closer monitoring.

Evaluation of false positives in the SARS-CoV-2 quantitative antigen test.

Ryo Kobayashi, Ryosei Murai, Mikako Moriai, Shinya Nirasawa, Hitoshi Yonezawa, Takashi Kondoh, Masachika Saeki, Yuki Yakuwa, Yuki Sato, Yuki Katayama, Hirotaka Nakafuri, Ikumi Kitayama, Koichi Asanuma, Yoshihiro Fujiya, Satoshi Takahashi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 10 ) 1477 - 1481 2021.10 [International journal]

INTRODUCTION: Highly sensitive reagents for detecting SARS-CoV-2 antigens have been developed for accurate and rapid diagnosis till date. In this study, we aim to clarify the frequency of false-positive reactions and reveal their details in SARS-CoV-2 quantitative antigen test using an automated laboratory device. METHODS: Nasopharyngeal swab samples (n = 4992) and saliva samples (n = 5430) were collected. We measured their SARS-CoV-2 antigen using Lumipulse® Presto SARS-CoV-2 Ag and performed a nucleic acid amplification test (NAAT) using the Ampdirect™ 2019 Novel Coronavirus Detection Kit as needed. The results obtained from each detection test were compared accordingly. RESULTS: There were 304 nasopharyngeal samples and 114 saliva samples were positive in the Lumipulse® Presto SARS-CoV-2 Ag test. All positive nasopharyngeal samples in the antigen test were also positive for NAAT. In contrast, only three (2.6%) of all the positive saliva samples in the antigen test were negative for NAAT. One showed no linearity with a dilute solution in the dilution test. Additionally, the quantitative antigen levels of all the three samples did not decrease after reaction with the anti-SARS-CoV-2 antibody. CONCLUSIONS: The judgment difference between the quantitative antigen test and NAAT seemed to be caused by non-specific reactions in the antigen test. Although the high positive and negative predictive value of this quantitative antigen test could be confirmed, we should consider the possibility of false-positives caused by non-specific reactions and understand the characteristics of antigen testing. We recommend that repeating centrifugation before measurement, especially in saliva samples, should be performed appropriately.

Significance of urinary liver-type fatty acid-binding protein in patients with normal renal function after undergoing intestinal urinary diversion: a preliminary study.

Takeshi Maehana, Koji Ichihara, Satoshi Takahashi, Yusuke Takahashi, Kohei Hashimoto, Toshiaki Tanaka, Naoya Masumori

Clinical and experimental nephrology 25 ( 10 ) 1151 - 1157 2021.10 [Domestic journal]

BACKGROUND: Liver-type fatty acid-binding protein (L-FABP) in urine is one of the early diagnostic biomarkers for acute and chronic kidney injuries. Although this protein is also identified in the intestine, there is no verified reference value for patients with intestinal urinary diversion (UD). The aim of the present study was to measure L-FABP values in such patients and compare them with the results for patients without UD. METHODS: Spot urine specimens were collected from 41 patients with UD and 50 subjects without UD with estimated glomerular filtration rates of over 60 ml/min/1.73 m2, and the L-FABP values were measured. The normal upper cutoff value in healthy subjects without UD is considered to be 7.24 μg/g Cr. First, the median values of the two groups were compared. Next, the subjects with negative proteinuria and without comorbidities associated with renal function were further selected and the median values of the groups were compared. RESULTS: The mean age was significantly higher in the UD group. The types of UD were ileal conduit (38 patients) and ileal neobladder (three patients). The median L-FABP value in the UD group was significantly higher than that in the non-diversion group (89.1 μg/g Cr vs. 2.0 μg/g Cr, p < 0.0001). After adjustment for their backgrounds, the median value remained higher in the UD group. CONCLUSIONS: L-FABP values in subjects with UD are higher than in those without UD. By this result, to develop a reference value in patients with intestinal UD population, further studies are required.

Clonal/subclonal changes and accumulation of CTX-M-type β-lactamase genes in fluoroquinolone-resistant Escherichia coli ST131 and ST1193 strains isolated during the past 12 years, Japan.

Yukari Fukushima, Toyotaka Sato, Naoyuki Tsukamoto, Chie Nakajima, Yasuhiko Suzuki, Satoshi Takahashi, Shin-Ichi Yokota

Journal of global antimicrobial resistance 27 150 - 155 2021.09 [International journal]

OBJECTIVES: Fluoroquinolone (FQ)- and third-generation cephalosporin-resistant Escherichia coli are increasing in Japan. In the early 2000s, the FQ-resistant E. coli clone ST131 increased in clinical settings worldwide. It frequently produces extended-spectrum β-lactamases (ESBLs) such as CTX-M. This study aimed to explore the characteristics of FQ-resistant E. coli isolated in Japan during 2008-2009 and 2020. METHODS: We compared FQ-resistant E. coli clinical isolates from urine samples collected in 2020 (151 isolates) with a FQ-resistant E. coli collection isolated in 2008-2009 (42 isolates). Identification of E. coli ST131 clades and blaCTX-M were determined by multiplex PCR. Sequence types of non-ST131 isolates were determined by whole-genome sequencing. RESULTS: Although the prevalence of ST131 was comparable in 2020 (74.2%) and 2008-2009 (78.6%), the subclades differed during the two time periods (C1-nM27: 40.2% in 2008-2009 vs. 78.8% in 2020; C1-M27: 32.1% in 2008-2009 vs. 9.1% in 2020). The incidence of blaCTX-M among ST131 isolates increased from 27.3% in 2008-2009 to 64.3% in 2020. blaCTX-M was found in 80.6% and 93.8% of C1-M27 and C2 in 2020, respectively, and blaCTX-M possession in C1-nM27 increased from 19.2% in 2008-2009 to 40% in 2020. FQ-resistant ST1193 was detected only in 2020 (17.9% of 151 isolates, of which 14.8% possessed blaCTX-M). CONCLUSION: Increased resistance of E. coli to FQs and third-generation cephalosporins in Japan can be attributed to the accumulation of blaCTX-M in C1-nM27 and the increase of C1-M27 and C2 clades with high blaCTX-M possession, alongside the spread of ST1193.

Nationwide surveillance of bacterial pathogens isolated from patients with acute uncomplicated cystitis in 2018: Conducted by the Japanese Research Group for Urinary Tract Infections (JRGU).

Koichiro Wada, Teruhiko Yokoyama, Satoshi Uno, Motoo Araki, Takuya Sadahira, Yuki Maruyama, Herik Acosta, Hirochika Nakajima, Yoshiki Hiyama, Yasuharu Kunishima, Yoshikazu Togo, Takuhisa Nukaya, Hiroki Yamada, Katsumi Shigemura, Shin Ito, Masanobu Tanimura, Kanao Kobayashi, Hiroyuki Kitano, Jun Teishima, Mitsuru Yasuda, Shinya Uehara, Ryoichi Hamasuna, Toyohiko Watanabe, Tohru Nakagawa, Hiroshi Hayami, Jun Miyazaki, Satoshi Takahashi, Naoya Masumori, Kiyohito Ishikawa, Hiroshi Kiyota, Masato Fujisawa, Soichi Arakawa, Yasutomo Nasu, Shingo Yamamoto

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 8 ) 1169 - 1180 2021.08 [International journal]

INTRODUCTION: The aim of this study was to monitor the development of drug-resistant bacteria isolated from acute uncomplicated cystitis (AUC) and to evaluate methodology of the survey conducted by collecting only clinical data. METHODS: We enrolled female patients at least 16 years of age diagnosed with AUC in 2018. Patient information including age, menopausal status, and results of bacteriological examination were collected and analyzed regardless of bacterial identification, antimicrobial susceptibility testing or extended-spectrum β-lactamase (ESBL) detection method. RESULTS: A total of 847 eligible cases were collected. Escherichia coli (E. coli) was the most frequently isolated bacterial species at about 70%, with proportions of fluoroquinolone-resistant E. coli (QREC) and ESBL-producing E. coli isolates at 15.6% and 9.5% of all E. coli isolates, respectively. The proportion of Staphylococcus saprophyticus (S. saprophyticus) was significantly higher in premenopausal women. Regarding the drug susceptibility of E. coli, isolates from Eastern Japan had significantly higher susceptibility to cefazolin, cefotiam and cefpodoxime and lower susceptibility to levofloxacin in postmenopausal women. ESBL-producing E. coli isolates had a high susceptibility to tazobactam-piperacillin, cefmetazole, carbapenems, aminoglycosides, and fosfomycin. In S. saprophyticus, the susceptibility to β-lactams including carbapenems was 40-60%. CONCLUSIONS: The proportions of QREC and ESBL-producing E. coli were increasing trends and lower susceptibility to LVFX in postmenopausal women was observed. Such surveillance, consisting of the collecting only clinical data, could be conducted easily and inexpensively. It is expected to be continuously performed as an alternative survey to conventional one collecting bacterial strains.

Early favipiravir treatment was associated with early defervescence in non-severe COVID-19 patients.

Satoshi Fujii, Yuta Ibe, Tomoyuki Ishigo, Hirotoshi Inamura, Yusuke Kunimoto, Yoshihiro Fujiya, Koji Kuronuma, Hiromasa Nakata, Masahide Fukudo, Satoshi Takahashi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 7 ) 1051 - 1057 2021.07 [International journal]

INTRODUCTION: The antiviral drug favipiravir has been shown to have in vitro antiviral activity against severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2). In this study, we investigated the clinical benefits and initiation of favipiravir treatment in patients with non-severe coronavirus-disease-2019 (COVID-19). METHODS: This study was a single-center retrospective cohort study. Receiver operating characteristic curves were drawn to calculate the area under the curve, and the optimal cut-off values for the time to initiate favipiravir treatment were calculated to predict defervescence within seven days. Univariate and multivariate Cox regression analyses were performed to identify potential influencing factors of defervescence. This was defined as a body temperature of less than 37 °C for at least 2 days. RESULTS: Data from 41 patients were used for the efficacy assessment. The days from the onset of fever to defervescence showed a positive correlation with the duration from the onset of fever to initiation of favipiravir treatment (r = 0.548, P < 0.001). The optimal cut-off value was the administration of favipiravir on day 4. Patients were assigned to two groups based on the optimal cut-off value from onset to initiation of favipiravir treatment: early treatment group (within 4-days) and late treatment group (more than 4-days). In the multivariate analysis, when adjusted for age, sex, and days from onset to initiation of favipiravir treatment, the significant factors were male sex and days of initiation of the favipiravir treatment. CONCLUSIONS: We recommend that if favipiravir is to be used for treatment, it should be initiated as early as possible.

Luteinizing hormone (LH) formed a complex with an immunoglobulin G caused abnormally high levels of LH: A case report.

Yoshifumi Umemori, Ryosei Murai, Koichi Asanuma, Yusuke Takahashi, Yoshika Kuno, Tsuyoshi Saito, Satoshi Takahashi

Clinical biochemistry 93 33 - 35 2021.07 [International journal]

We encountered a 30-year-old woman with remarkably elevated luteinizing hormone (LH) levels, as measured by electrochemiluminescent immunoassay (ECLIA), and no specific symptoms. We performed the following investigations: dilution linearity test, polyethylene glycol (PEG) precipitation test, immunoprecipitation test, protein G addition test, and high-performance liquid chromatography (HPLC) analysis. The linearity of patient's serum was similar to that of a standard LH preparation, and non-specific reactions were not observed. The recovery rate of LH shown by the PEG precipitation test, immunoprecipitation test, and protein G addition test was low. Moreover, an abnormal peak in HPLC was located at a slightly larger molecular weight position than that of IgG. These results showed the presence of macro-LH, LH, and anti-LH-IgG autoantibody complex and suggested that the clearance of LH from the blood was delayed due to IgG binding, and therefore, the LH value was falsely high. We should keep the possibility of macro-LH in mind in cases of unexpectedly high LH values.

Evaluation of two commercial molecular diagnostic assays: The Xpert Norovirus and the TRCReady NV.

Yuki Sato, Shinya Nirasawa, Masachika Saeki, Yuki Yakuwa, Mayumi Ono, Nozomi Yanagihara, Yoshihiro Fujiya, Satoshi Takahashi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 7 ) 1115 - 1118 2021.07 [International journal]

INTRODUCTION: Norovirus is highly contagious, and a few particles of this virus are sufficient to make people sick. It is desirable to develop quick and accurate laboratory methods to detect norovirus. METHODS: We evaluated two commercial molecular diagnostic assays, the Xpert Norovirus and the TRCReady NV, using clinical fecal samples. A reference method was performed using in-house real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR). RESULTS: The results of the real-time RT-PCR analysis of 60 suspected cases of norovirus infection showed 5 cases of Genogroup I (GI) positives and 21 cases of GII positives, among which was 1 GI and GII coinfection. The viral titers of the norovirus-positive samples ranged from 1.54 × 101 to 3.14 × 108 copies/μL. Norovirus GII.17 (12 cases, 48%) was the most frequently detected genotype in this study, followed by GII.4 (6 cases, 24%), GII.13 (2 cases, 8%), GI.2 (2 cases, 8%), GI.3 (2 cases, 8%), GI.1 (1 case, 4%), and GII.2 (1 case, 4%). The kappa coefficient was 1.000 (95% CI: 1.000-1.000) for Xpert Norovirus and 0.966 (95% CI: 0.896-1.000) for TRCReady NV, indicating a strong agreement. CONCLUSIONS: Norovirus detection using Xpert Norovirus and TRCReady NV is highly useful for diagnosis and infection control because these assays are easy to operate, quick, and exhibit almost the same performance as that of real-time RT-PCR.

Invasive pneumococcal disease affected the fatal outcome in a COVID-19 patient.

Koji Kuronuma, Naofumi Bunya, Bin Chang, Yoshihiro Fujiya, Kazunori Oishi, Eichi Narimatsu, Satoshi Takahashi, Hirofumi Chiba

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 7 ) 1108 - 1111 2021.07 [International journal]

A 68-year-old man experienced fever and cough and was referred to a hospital for day 4. He had a positive reverse transcription-polymerase chain reaction result for severe acute respiratory syndrome coronavirus-2. On day 12, his PaO2/FiO2 ratio worsened to 120 and he was transferred to Sapporo Medical University Hospital for treatment using extracorporeal membrane oxygenation. Venous blood cultures were positive for Streptococcus pneumoniae, which were serotype 3, mucoid-type, and penicillin susceptible. Coinfections with coronavirus disease-2019 and invasive pneumococcal disease are rare; however, they are associated with a higher case fatality than either of the conditions manifesting alone.

Gender-affirming hormone treatment causes changes in gender phenotype in a 12-lead electrocardiogram.

Nagomi Saito, Daigo Nagahara, Koji Ichihara, Naoya Masumori, Tetsuji Miura, Satoshi Takahashi

Heart rhythm 18 ( 7 ) 1203 - 1209 2021.07 [International journal]

BACKGROUND: Men and women have specific patterns in an electrocardiogram (ECG) differentiated by J-point elevation and ST-segment angle. Although gender-affirming hormone treatment is one of the treatments for gender dysphoria, its influence on an ECG has not been clarified yet. OBJECTIVE: The purpose of this study was to investigate ECG changes induced by gender-affirming hormone treatment. METHODS: The study population consisted of 29 transgender males and 8 transgender females and 37 age- and sex-matched cisgender females and males. Male pattern was defined as J-point elevation > 0.1 mV and ST-segment angle > 20° in precordial leads. RESULTS: In the comparison between 29 transgender males and cisgender females, the prevalence of the male pattern (89.7% vs 6.9%; P < .001), prevalence of the early repolarization pattern (51.7% vs 17.2%; P = .01), J-point elevation (leads V1-V6), T-wave amplitudes (leads V1-V6), QRS amplitudes (leads II, III, V1-V6), and P-wave amplitudes (leads V1-V3) were significantly higher in transgender males. The prevalence of the male pattern was lower in transgender females than in cisgender males (25.0% vs 87.5%; P = .04). In the analysis of transgender males for whom ECGs were available before and after gender-affirming hormone treatment (n = 13), J-point elevation and T-wave amplitudes significantly increased after gender-affirming hormone treatment, leading to a higher prevalence of the male pattern (23.1% vs 92.3%; P < .001). The prevalence of the early repolarization pattern and QRS amplitudes also significantly increased after the treatment, but the augmentation of P-wave amplitudes was modest. CONCLUSION: Gender-affirming hormone treatment for gender dysphoria is accompanied by a change in ECG phenotype toward affirming gender, in which change in androgen level may be involved.

Evaluating a novel, highly sensitive, and quantitative reagent for detecting SARS-CoV-2 antigen.

Ryo Kobayashi, Ryosei Murai, Koichi Asanuma, Yoshihiro Fujiya, Satoshi Takahashi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 6 ) 800 - 807 2021.06 [International journal]

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is rapidly spreading all over the world. A new quantifying reagent for detecting SARS-CoV-2 antigen was developed for early and accurate detection. We evaluated the novel quantitative reagent for detecting SARS-CoV-2 antigen using an automated laboratory device. METHODS: One-hundred nasopharyngeal samples were collected from 47 SARS-CoV-2-infected patients, and 200 samples were collected from healthy donners. We measured the SARS-CoV-2 antigen and nucleic acid using Lumipulse Presto SARS-CoV-2 Ag and the 2019 Novel Coronavirus Detection Kit, respectively. RESULTS: The sensitivity and specificity of the SARS-CoV-2 antigen test were 75.7% (56/74) and 96.0% (192/200), respectively. The concordance rate in the positive group between the antigen and nucleic acid tests was 66% (66/100). In addition, the correlation coefficient between the concentration of SARS-CoV-2 antigen and the level of SARS-CoV-2 RNA was 0.74. There were 19 discrepant samples in which SARS-CoV-2 RNA was detected without SARS-CoV-2 antigen. There was significant difference between the discrepant and matched samples in terms of the time since symptom onset: the 19 discrepant samples were collected a median of 33 days after onset, while the 55 matched samples were collected a median of 19 days after onset. In addition, the 19 discrepant samples were collected from patients who were immune against SARS-CoV-2. CONCLUSIONS: This novel SARS-CoV-2 antigen detection assay is highly sensitive, rapid, accurate, easily diagnostic. It may be useful in both clinical diagnosis and in screening because it does not require special methods such as PCR.

The JAID/JSC guidelines to Clinical Management of Infectious Disease 2017 concerning male urethritis and related disorders.

Ryoichi Hamasuna, Mitsuru Yasuda, Satoshi Takahashi, Shinya Uehara, Yasuhiro Kawai, Isao Miyairi, Soichi Arakawa, Hiroshi Kiyota

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 4 ) 546 - 554 2021.04 [International journal]

A Clinical Trial Evaluating the Usefulness of Tailored Antimicrobial Prophylaxis Using Rectal-culture Screening Media Prior to Transrectal Prostate Biopsy: A Multicenter, Randomized Controlled Trial.

Takuya Sadahira, Yuki Maruyama, Yoshiki Hiyama, Hiroyuki Kitano, Hiroki Yamada, Takayuki Goto, Tsubasa Kondo, Katsumi Shigemura, Yosuke Mitsui, Takehiro Iwata, Kohei Edamura, Motoo Araki, Masami Watanabe, Tadasu Takenaka, Jun Teishima, Yasuyoshi Miyata, Kiyohito Ishikawa, Ei-Ichiro Takaoka, Jun Miyazaki, Satoshi Takahashi, Naoya Masumori, Hiroshi Kiyota, Masato Fujisawa, Shingo Yamamoto, Takafumi Sakuma, Norihiro Kusumi, Takaharu Ichikawa, Toyohiko Watanabe, Yoshitsugu Nasu, Masaya Tsugawa, Yasutomo Nasu, Koichiro Wada

Acta medica Okayama 75 ( 5 ) 663 - 667 2021 [Domestic journal]

The aim of this report is to introduce an on-going, multicenter, randomized controlled trial to evaluate whether tailored antimicrobial prophylaxis guided by rectal culture screening prevents acute bacterial prostatitis following transrectal prostate biopsy (TRPB). Patients will be randomized into an intervention or non-intervention group; tazobactam-piperacillin or levofloxacin will be prophylactically administered according to the results of rectal culture prior to TRPB in the intervention group whereas levofloxacin will be routinely given in the non-intervention group. The primary endpoint is the occurrence rate of acute bacterial prostatitis after TRPB. Recruitment begins in April, 2021 and the target total sample size is 5,100 participants.

Emergence of the Novel Aminoglycoside Acetyltransferase Variant aac(6')-Ib-D179Y and Acquisition of Colistin Heteroresistance in Carbapenem-Resistant Klebsiella pneumoniae Due to a Disrupting Mutation in the DNA Repair Enzyme MutS.

Toyotaka Sato, Takayuki Wada, Suguru Nishijima, Yukari Fukushima, Chie Nakajima, Yasuhiko Suzuki, Satoshi Takahashi, Shin-Ichi Yokota

mBio 11 ( 6 ) 2020.12 [International journal]

Amikacin and colistin are effective against carbapenem-resistant Klebsiella pneumoniae In 2017, we successively isolated three carbapenem-resistant K. pneumoniae isolates (ST967) from a patient with chronic renal failure in Japan. The first (SMKP01, sputum, day 0) and second (SMKP02, blood, day 14) strains were resistant to most antimicrobials tested but still susceptible to amikacin (MICs of 4 and 0.5 mg/liter, respectively) and colistin (MIC of 0.5 mg/liter for both). The third strain (SMKP03, blood, day 51) was not susceptible to amikacin (MIC, 32 mg/liter), and its MIC for colistin varied (0.5 to 8 mg/liter). Whole-genome sequencing of SMKP01 revealed that 17 of 20 antimicrobial resistance genes, including qnrB91 (a novel qnrB2 variant) and aac(6')-Ib-cr, were located on an 86.9-kb IncFII-IncQ plasmid. The qnrB91 conferred greater fluoroquinolone resistance than qnrB2 SMKP03 aac(6')-Ib-cr that possessed a gene mutation that resulted in an R102W substitution, namely, aac(6')-Ib-D179Y, made a greater contribution to amikacin resistance than did aac(6')-Ib-cr SMKP03 harbored a nonsense mutation in mutS, which encodes a DNA repair enzyme. Introduction of this mutation into SMKP01 (SMKP01mutSA307T) resulted in a dramatic increase (>58-fold) in the frequency of spontaneous amikacin-resistant mutants relative to SMKP01, and the substantial mutants possessed aac(6')-Ib-D179Y SMKP01mutSA307T exhibited an unstable MIC for colistin (0.5 to 8 mg/liter). The results demonstrate that a disruptive mutation in MutS, arising during the clinical course of an infection, created a platform for the acquisition of amikacin nonsusceptibility and colistin heteroresistance in multidrug-resistant K. pneumoniae, mediated by the elevated frequency of spontaneous mutations.IMPORTANCE The emergence of multidrug resistance in pathogens such as Klebsiella pneumoniae is of great clinical concern. Antimicrobial resistance sometimes arises during the course of an infection. Although many studies have reported the emergence of antimicrobial resistance and novel antimicrobial resistance genes in the clinical isolates, the identity of the bacterial factor(s) that generate this emergence is still unclear. We report that a disruptive mutation in MutS, arising during the clinical course of an infection, created a context for the acquisition of colistin resistance and the emergence of a novel variant of the amikacin resistance gene in multidrug-resistant K. pneumoniae via an increase in the frequency of spontaneous mutation. This observation is important for understanding how K. pneumoniae develops multidrug resistance during infection and could potentially lead to new antimicrobial treatments for high-risk pathological microbes.

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