Published Papers - YAMAMOTO KAZUKO

A case of tocilizumab-refractory idiopathic multicentric Castleman's disease successfully treated with sirolimus.

Remi Sumiyoshi, Tomohiro Koga, Kaori Furukawa, Masataka Umeda, Kazuko Yamamoto, Ryoichi Mori, Atsushi Kawakami

Clinical immunology (Orlando, Fla.) ( Clinical Immunology )  233   108887 - 108887   2021.12 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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mTOR signaling may be a new therapeutic target for IL-6 inhibitor refractory iMCD-NOS.

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Removal of an aspirated tooth from the bronchus using a cryoprobe: A case report.

Hiroshi Ishimoto, Noriho Sakamoto, Sakiko Moriyama, Mayako Murata, Nana Nakada, Atsuko Hara, Takashi Kido, Hiroyuki Yamaguchi, Kazuko Yamamoto, Yasushi Obase, Yuji Ishimatsu, Hiroshi Mukae

Respirology case reports   9 ( 12 ) e0880   2021.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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An 88-year-old bedridden man with Alzheimer's disease developed fever and hypoxaemia. Chest radiography showed obstructive pneumonia caused by a foreign body in the airway. Examination using a flexible bronchoscope revealed a silver-crowned molar, thought to have fallen out due to root caries, at the left lower lobe branch. Removal of the foreign body was unsuccessful with grasping or basket forceps, but successful with cryoadhesion using a cryoprobe. Removal of an airway foreign body by a cryoprobe depends on the nature of the foreign body, namely its water content. Therefore, cryoprobes are not inherently suitable for removing foreign bodies of aspirated teeth, but a tooth covered with mucus for a long time after aspiration can be cryoadhered with cryoprobes. Airway foreign bodies that remain in the airway for a long time should also be considered for removal by cryoprobe, regardless of the water content of the material.

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Association between the psoas muscle index and hospitalization for pneumonia in patients undergoing hemodialysis.

Kosei Yamaguchi, Mineaki Kitamura, Takahiro Takazono, Shuntaro Sato, Kazuko Yamamoto, Satoko Notomi, Kenji Sawase, Takashi Harada, Satoshi Funakoshi, Hiroshi Mukae, Tomoya Nishino

BMC nephrology ( BMC Nephrology )  22 ( 1 ) 394 - 394   2021.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: Although muscle mass loss and pneumonia are common and crucial issues in hemodialysis (HD) patients, few reports have focused on their association, which remains unclear. This study assessed the association between skeletal muscle mass and the incidence of pneumonia in HD patients using the psoas muscle index (PMI). METHODS: This retrospective study included 330 patients on HD who were treated at a single center between July 2011 and June 2012. The observation period was between July 2011 and June 2021. Demographic, clinical, and HD data were collected, and the associations between PMI and hospitalization due to bacterial pneumonia were evaluated using Cox proportional hazards models adjusted for patients' background data. Additionally, the correlation between patient characteristics and PMI was evaluated using multivariable linear regression. RESULTS: Among 330 patients (mean age, 67.3 ± 13.3; 56.7% male; median dialysis vintage 58 months, (interquartile range [IQR] 23-124), 79 were hospitalized for pneumonia during the observation period (median observation period was 4.5 years [IQR 2.0-9.1]). The multivariable Cox proportional analysis, which was adjusted for age, sex, dialysis vintage, diabetes mellitus, and stroke history and considered death as a competing risk, indicated that decreased PMI/(standard deviation) was closely associated with the development of pneumonia (hazard ratio: 0.67, 95% confidence interval: 0.47-0.95, p = 0.03). CONCLUSIONS: Skeletal muscle mass was associated with the development of pneumonia in patients on HD and could be a useful marker for the risk of pneumonia.

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HLA-B54 is an independent risk factor for pneumonia in Japanese patients with interstitial lung disease: A multicenter retrospective cohort study.

Noriho Sakamoto, Hiroshi Ishimoto, Masahiro Tahara, Takashi Kido, Atsuko Hara, Takuto Miyamura, Daisuke Okuno, Takatomo Tokito, Sumako Yoshioka, Shimpei Morimoto, Takahiro Takazono, Kazuko Yamamoto, Hiroyuki Yamaguchi, Yasushi Obase, Yuji Ishimatsu, Kazuhiro Yatera, Hiroshi Mukae

Respiratory medicine   188   106612 - 106612   2021.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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PURPOSE: Pneumonia is a major cause of respiratory-related hospitalization and an important prognostic factor in patients with chronic interstitial lung disease (ILD). However, the relationship between the incidence of pneumonia and human leukocyte antigen (HLA) serotype has not been fully elucidated. Therefore, this study aimed to determine if there is a relationship between HLA serotype and the incidence of pneumonia in Japanese patients with ILD. METHODS: The medical records of patients with ILD treated at any of three centers in Japan were reviewed to determine their HLA-A and HLA-B serotypes. The characteristics of patients with and without pneumonia were compared. Cox regression analysis was performed to identify risk factors for pneumonia and death in these patients. RESULTS: One hundred and forty-four patients with ILD (pneumonia group, n = 27; non-pneumonia group, n = 117) and complete HLA serology data available were included. HLA-B54 positivity was significantly more common in the pneumonia group than in the non-pneumonia group (37.0% vs. 15.4%, p = 0.010). HLA-B54 positivity was also a significant risk factor for pneumonia (hazard ratio [HR] 4.166, 95% confidence interval [CI] 1.862-9.320, p = 0.001) and death (HR 4.050, 95% CI 1.581-10.374, p = 0.004) in patients with ILD. Furthermore, HLA-B54 positivity was a significant risk factor for pneumonia (HR 3.964, 95% CI 1.392-11.090, p = 0.010) and death (HR 8.131, 95% CI 1.763-37.494, p = 0.007) in patients with idiopathic pulmonary fibrosis. CONCLUSION: HLA-B54 positivity was a significant risk factor for pneumonia and death in patients with ILD, including those with idiopathic pulmonary fibrosis.

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Discrepancy of SARS-CoV-2 PCR results due to the sample collection sites and possible improper sampling.

Satoshi Irifune, Nobuyuki Ashizawa, Takahiro Takazono, Pierre Mutantu, Takeshi Nabeshima, Mya Myat Ngwe Tun, Kenji Ota, Tatsuro Hirayama, Ayumi Fujita, Masato Tashiro, Takeshi Tanaka, Kazuko Yamamoto, Yoshifumi Imamura, Taiga Miyazaki, Toyomitsu Sawai, Koichi Izumikawa, Katsunori Yanagihara, Kouichi Morita, Hiroshi Mukae

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   27 ( 10 ) 1525 - 1528   2021.10 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Polymerase chain reaction (PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is necessary for confirming a diagnosis of Coronavirus disease 2019 (COVID-19). Here we present a COVID-19 case of an elderly woman whose SARS-CoV-2 PCR tests showed false negative repeatedly by evaluating with different sampling sites and procedures. Nasopharyngeal swabs, suctioned sputum, and tongue swabs were collected for SARS-CoV-2-PCR. As for tongue swabs, we compared between two different sample conditions; one obtained with dry condition and the other obtained with moistened condition inside the oral cavity. SARS-CoV-2-PCR showed positive for an extended period with suctioned sputum samples compared with nasopharyngeal swabs and tongue swabs. No SARS-CoV-2 from a nasopharyngeal swab sample obtained on day 46 after symptoms onset was isolated despite high viral load (183740.5 copies/5μL). An adequate production of neutralizing antibody in a serum sample on day 46 was also confirmed. The number of RNA copies of the tongue swab samples was higher with moistened condition than with dry condition. The present case suggests that the difference of sampling site or sample condition can affect PCR results. High loads viral RNA detection does not always correlate with infectivity.

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A case of Lemierre's syndrome with double vision as the first symptom.

Koki Fukushima, Takahiro Takazono, Nobuyuki Ashizawa, Shintaro Hara, Kyoko Kitaoka, Reiko Ideguchi, Teiichiro Miyazaki, Tatsuro Hirayama, Kazuko Yamamoto, Yoshifumi Imamura, Taiga Miyazaki, Koichi Izumikawa, Hiroshi Mukae

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy ( Journal of Infection and Chemotherapy )  28 ( 2 ) 286 - 289   2021.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Lemierre's syndrome is a serious disease that typically causes oropharyngeal infection with internal jugular vein thrombosis, followed by distant infection focus, such as septic pulmonary embolism. The main causative organisms are anaerobic bacteria in the oral cavity, namely Fusobacterium necrophorum. We encountered an extremely rare case of Lemierre's syndrome, where double vision was found to be the first symptom. The patient's blood culture results showed the presence of F. nucleatum, which spread from the sphenoid sinus to the skull base because of chronic sinusitis; the patient presented with longus colli abscess, clivus osteomyelitis, venous thrombosis, and hematogenous infection. Antibiotic treatment with sulbactam/ampicillin was continued for 14 weeks, and no recurrence has been observed so far. Lemierre's syndrome can be complicated with atypical symptoms such as double vision if the cranial nerves are involved. It might be important to consider this disease in the differential diagnosis in the presence of cranial nerve symptoms of unknown origin with fever or inflammatory findings.

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Association between Serum Phosphate Levels and the Development of Aortic Stenosis in Patients Undergoing Hemodialysis

Miki Torigoe, Mineaki Kitamura, Kosei Yamaguchi, Takumi Uchino, Kenta Torigoe, Takashi Harada, Satoshi Funakoshi, Kazuko Yamamoto, Koji Maemura, Kiyoyuki Eishi, Hiroshi Mukae, Tomoya Nishino

Journal of Clinical Medicine ( MDPI AG )  10 ( 19 ) 4385 - 4385   2021.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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We aimed to investigate the factors associated with the development of aortic stenosis (AS) in patients undergoing hemodialysis (HD), and to elucidate the prognosis of HD patients with AS. Patients on HD that had also undergone echocardiography at Nagasaki Renal Center between July 2011 and June 2012 were included. Patients with AS at the time of inclusion were excluded. The diagnosis of AS was based on an annual routine or additional echocardiography. The patients were followed up until June 2021. The association between patient background and AS was also evaluated. Of the 302 patients (mean age, 67.4 ± 13.3 years; male, 58%; median dialysis history, 4.7 years), 60 developed AS and 10 underwent aortic valve replacement. A Cox proportional hazards model revealed that age (hazard ratio (HR), 1.07; 95% confidential interval (CI), 1.04–1.10; p < 0.001) and serum phosphate levels (HR, 1.40; 95%CI, 1.16–1.67, p < 0.001) were independent risk factors for developing AS. Incidentally, there was no significant mortality difference between patients with AS and those without (p = 0.53). Serum phosphate levels are a risk factor for developing AS and should be controlled. Annual echocardiography may contribute to the early detection of AS and improves the prognosis of patients undergoing HD.

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Efficacy of clarithromycin in patients with mild COVID-19 pneumonia not receiving oxygen administration: protocol for an exploratory, multicentre, open-label, randomised controlled trial (CAME COVID-19 study).

Kazuko Yamamoto, Naoki Hosogaya, Noriho Sakamoto, Haruo Yoshida, Hiroshi Ishii, Kazuhiro Yatera, Koichi Izumikawa, Katsunori Yanagihara, Hiroshi Mukae

BMJ open   11 ( 9 ) e053325   2021.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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INTRODUCTION: The COVID-19 pandemic has emerged worldwide. Although several medications have been approved for treating moderate-to-severe COVID-19, very few treatment strategy has been established for patients with mild COVID-19 who do not require oxygen administration. Clarithromycin is a macrolide antimicrobial agent that has been widely used for bacterial respiratory infectious diseases. Clarithromycin also acts an immunomodulating drug and suppresses cytokine storms in viral respiratory diseases, including influenza. In this study, we aim to evaluate the efficacy of clarithromycin in patients with mild COVID-19. METHODS AND ANALYSIS: This is an exploratory, multicentre, open-label, randomised controlled trial. This study was initiated in May 2021 and will end in July 2022. Patients with mild COVID-19 pneumonia who do not require oxygen administration will be enrolled and randomly assigned in a 1:1:1 ratio to group A (administration of clarithromycin 800 mg/day), group B (administration of clarithromycin 400 mg/day) or group C (standard treatment without clarithromycin). The planned number of enrolled patients is 60 (20 patients × three groups). The primary endpoint is the number of days required to improve the clinical symptoms as measured by the severity score. Secondary endpoints include days for recovery of the body temperature, proportion of patients with oxygen administration, inflammatory cytokines, viral load, serum immunoglobulins, peripheral blood lymphocytes, blood biomarkers and pneumonia infiltrations. ETHICS AND DISSEMINATION: The study protocol was approved by the Clinical Research Review Board of Nagasaki University in accordance with the Clinical Trials Act in Japan. The study will be conducted in accordance with the Declaration of Helsinki, the Clinical Trials Act and other current legal regulations in Japan. Written informed consent will be obtained from all the participants. The results of this study will be reported as journal publications. TRIAL REGISTRATION NUMBER: jRCTs071210011.

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Correction to: Clinical and experimental phenotype of azole-resistant Aspergillus fumigatus with a HapE splice site mutation: a case report.

Yuya Ito, Takahiro Takazono, Satoru Koga, Yuichiro Nakano, Nobuyuki Ashizawa, Tatsuro Hirayama, Masato Tashiro, Tomomi Saijo, Kazuko Yamamoto, Yoshifumi Imamura, Taiga Miyazaki, Katsunori Yanagihara, Koichi Izumikawa, Hiroshi Mukae

BMC infectious diseases   21 ( 1 ) 961 - 961   2021.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Assessment of oral health in elderly patients with dementia by measuring volatile sulfur compounds and its relationship with pneumonia development: A pilot study.

Satoru Koga, Takahiro Takazono, Takumi Serita, Nobuyuki Ashizawa, Tatsuro Hirayama, Masato Tashiro, Naoki Hosogaya, Kazuko Yamamoto, Yoshifumi Imamura, Hiroyuki Yamaguchi, Noriho Sakamoto, Yasushi Obase, Katsunori Yanagihara, Koichi Izumikawa, Hiroshi Mukae

Respiratory investigation ( Respiratory Investigation )  60 ( 1 ) 162 - 166   2021.09 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: This study aimed to clarify the involvement of anaerobes in aspiration pneumonia by measuring volatile sulfur compounds (VSCs), which are metabolites of anaerobic bacteria in the mouth. METHODS: This study included 84 older adult patients (mean age, 82.5 ± 7.34 years) who had dementia and were hospitalized for more than 6 months. We measured the VSCs in the patient's mouth with Oral Chroma and obtained the data of pneumonia development in the past 6 months. We also evaluated the association or correlation of VSCs and some factors which might be the risk factors of aspiration pneumonia. RESULTS: The development of pneumonia had no significant association with the VSCs in the patient's mouth. CONCLUSION: The present pilot study suggests that anaerobes might not be the main causative pathogens of aspiration pneumonia in older adult patients.

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Infectious Pneumonia and Lower Airway Microorganisms in Patients with Rheumatoid Arthritis.

Shuhei Ideguchi, Kazuko Yamamoto, Masahiro Tahara, Tomohiro Koga, Shotaro Ide, Tatsuro Hirayama, Takahiro Takazono, Yoshifumi Imamura, Taiga Miyazaki, Noriho Sakamoto, Shimpei Morimoto, Koichi Izumikawa, Katsunori Yanagihara, Kazuto Ashizawa, Takatoshi Aoki, Atsushi Kawakami, Kazuhiro Yatera, Hiroshi Mukae

Journal of clinical medicine   10 ( 16 )   2021.08 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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The relationship between microorganisms present in the lower respiratory tract and the subsequent incidence of pneumonia in patients with rheumatoid arthritis is unclear. A retrospective cohort study was designed to include a total of 121 patients with rheumatoid arthritis who underwent bronchoscopy at three hospitals between January 2008 and December 2017. Data on patient characteristics, microorganisms detected by bronchoscopy, and subsequent incidences of pneumonia were obtained from electronic medical records. Patients were divided into groups based on the microorganisms isolated from the lower respiratory tract. The cumulative incidence of pneumonia was assessed using the Kaplan-Meier method, and decision tree analysis was performed to analyze the relation between the presence of microorganisms and the occurrence of pneumonia. The most frequently isolated microbes were Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae. Patients whose samples tested negative for bacteria or positive for normal oral flora were included in the control group. The rate of the subsequent incidence of pneumonia was higher in the P. aeruginosa group than in the control group (p = 0.026), and decision tree analysis suggested that P. aeruginosa and patient performance status were two important factors for predicting the incidence of pneumonia. In patients with rheumatoid arthritis, the presence of P. aeruginosa in the lower respiratory tract was associated with the subsequent incidence of pneumonia.

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Evaluation of four commercial severe acute respiratory coronavirus 2 antibody tests.

Nobuyuki Ashizawa, Takahiro Takazono, Kaname Ohyama, Yoji Nagasaki, Masaki Okamoto, Tatsuro Hirayama, Kensuke Takahashi, Hirotomo Yamanashi, Masato Tashiro, Naoki Hosogaya, Takeshi Tanaka, Kazuko Yamamoto, Yuichi Fukuda, Yoshifumi Imamura, Toshinori Kawanami, Taiga Miyazaki, Toyomitsu Sawai, Kiyoyasu Fukushima, Kazuhiro Yatera, Katsunori Yanagihara, Koichi Izumikawa, Hiroshi Mukae

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   27 ( 7 ) 1033 - 1038   2021.07 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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INTRODUCTION: Numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests exists commercially; however, their performance using clinical samples is limited. Although insufficient to detect SARS-CoV-2 in the early phase of infection, antibody assays can be of great use for surveillance studies or for some coronavirus disease 2019 (COVID-19) patients presenting late to the hospital. METHODS: This study evaluated the sensitivity and specificity of four commercial SARS-CoV-2 lateral flow antibody tests using 213 serum specimens from 90 PCR-positive confirmed COVID-19 patients. Of 59 negative control sera, 50 were obtained from patients with other respiratory infectious diseases before COVID-19 pandemic began while nine were from patients infected with other respiratory viruses, including two seasonal coronaviruses. RESULTS: The varied sensitivities for the four commercial kits were 70.9%, 65.3%, 45.1%, and 65.7% for BioMedomics, Autobio Diagnostics, Genbody, and KURABO, respectively, between sick days 1 and 155 in COVID-19 patients. The sensitivities of the four tests gradually increased over time after infection before sick day 5 (15.0%, 12.5%, 15.0%, and 20.0%); from sick day 11-15 (95.7%, 87.2%, 53.2%, and 89.4%); and after sick day 20 (100%, 100%, 68.6%, and 96.1%), respectively. For severe illness, the sensitivities were quite high in the late phase after sick day 15. The specificities were over 96% for all four tests. No cross-reaction due to other pathogens, including seasonal coronaviruses, was observed. CONCLUSIONS: Our results demonstrated the large differences in the antibody test performances. This ought to be considered when performing surveillance analysis.

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Clinical and experimental phenotype of azole-resistant Aspergillus fumigatus with a HapE splice site mutation: a case report.

Yuya Ito, Takahiro Takazono, Satoru Koga, Yuichiro Nakano, Nobuyuki Ashizawa, Tatsuro Hirayama, Masato Tashiro, Tomomi Saijo, Kazuko Yamamoto, Yoshifumi Imamura, Taiga Miyazaki, Katsunori Yanagihara, Koichi Izumikawa, Hiroshi Mukae

BMC infectious diseases ( BMC Infectious Diseases )  21 ( 1 ) 573 - 573   2021.06 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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BACKGROUND: The recent increase in cases of azole-resistant Aspergillus fumigatus (ARAf) infections is a major clinical concern owing to its treatment limitations. Patient-derived ARAf occurs after prolonged azole treatment in patients with aspergillosis and involves various cyp51A point mutations or non-cyp51A mutations. The prognosis of patients with chronic pulmonary aspergillosis (CPA) with patient-derived ARAf infection remains unclear. In this study, we reported the case of a patient with ARAf due to HapE mutation, as well as the virulence of the isolate. CASE PRESENTATION: A 37-year-old male was presented with productive cough and low-grade fever. The patient was diagnosed with CPA based on the chronic course, presence of a fungus ball in the upper left lobe on chest computed tomography (CT), positivity for Aspergillus-precipitating antibody and denial of other diseases. The patient underwent left upper lobe and left S6 segment resection surgery because of repeated haemoptysis during voriconazole (VRC) treatment. The patient was postoperatively treated with VRC for 6 months. Since then, the patient was followed up without antifungal treatment but relapsed 4 years later, and VRC treatment was reinitiated. Although an azole-resistant isolate was isolated after VRC treatment, the patient did not show any disease progression in either respiratory symptoms or radiological findings. The ARAf isolated from this patient showed slow growth, decreased biomass and biofilm formation in vitro, and decreased virulence in the Galleria mellonella infection model compared with its parental strain. These phenotypes could be caused by the HapE splice site mutation. CONCLUSIONS: This is the first to report a case demonstrating the clinical manifestation of a CPA patient infected with ARAf with a HapE splice site mutation, which was consistent with the in vitro and in vivo attenuated virulence of the ARAf isolate. These results imply that not all the ARAf infections in immunocompetent patients require antifungal treatment. Further studies on the virulence of non-cyp51A mutations in ARAf are warranted.

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Erythema induratum of Bazin-A subcutaneous granulomatous vasculitis that caused difficulty in walking.

Satoshi Irifune, Kazuko Yamamoto, Sosuke Ishijima, Yuta Koike, Junya Fukuoka, Hiroshi Mukae

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases   106   183 - 184   2021.05 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Transition of triazole-resistant Aspergillus fumigatus isolates in a Japanese tertiary hospital and subsequent genetic analysis.

Takahiro Takazono, Yuya Ito, Masato Tashiro, Yuichiro Nakano, Tatsuro Hirayama, Naoki Hosogaya, Tomomi Saijo, Kazuko Yamamoto, Yoshifumi Imamura, Taiga Miyazaki, Katsunori Yanagihara, Shigeru Kohno, Hiroshi Mukae, Koichi Izumikawa

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   27 ( 3 ) 537 - 539   2021.03 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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OBJECTIVE: To evaluate the annual variation in the frequency of patient-acquired azole-resistant Aspergillus fumigatus (ARAf), and correlate it to the amount of oral triazole prescribed, in Nagasaki, Japan. METHODS: A. fumigatus isolates from respiratory specimens collected in the Nagasaki University Hospital (NUH) between 1996 and 2017 were included in the study. The amount of oral triazole prescribed in NUH since 2001 was obtained from the medical ordering system. Mutations in cyp51A, hmg1, and erg6 genes of ARAf were also analysed. RESULTS: From a total of 240 ARAf strains, 12 (5%), 6 (2.5%), 15 (6.25%), and 3 (1.25%) strains were resistant to itraconazole (ITC), voriconazole (VRC), to either ITC or VRC, and both triazoles, respectively. The amount of prescribed VRC increased annually, and was three times as large as that of ITC in 2017. All eleven patients harbouring ITC-resistant strains had a history of prior ITC treatment, while only one of six patients harbouring VRC-resistant strains had a history of prior VRC treatment. cyp51A mutations were recorded in 10 strains; however, tandem repeat mutations of the promoter region of cyp51A were not observed. Several azole-resistant strains had non-cyp51A mutations. CONCLUSIONS: The frequency of patient-acquired ARAf is not increasing in Nagasaki, Japan. Furthermore, the prevalence of VRC-induced ARAf was rare despite the remarkable increase in the amount of prescribed VRC. Mutations in genes other than cyp51A should also be considered when ARAf strains are obtained from patients treated with azole antifungals.

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Effects of surgical masks on droplet dispersion under various oxygen delivery modalities.

Takahiro Takazono, Kazuko Yamamoto, Ryuta Okamoto, Shimpei Morimoto, Koichi Izumikawa, Hiroshi Mukae

Critical care (London, England)   25 ( 1 ) 89 - 89   2021.02 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Duration of antifungal therapy for septic pulmonary embolism caused by Candida albicans from a central venous catheter: A case report.

Daisuke Okuno, Kazuhiro Oshima, Taiga Miyazaki, Nobuyuki Ashizawa, Tatsuro Hirayama, Takahiro Takazono, Tomomi Saijo, Kazuko Yamamoto, Yoshifumi Imamura, Hiroyuki Yamaguchi, Noriho Sakamoto, Yasushi Obase, Koichi Izumikawa, Katsunori Yanagihara, Hiroshi Mukae

Clinical case reports   9 ( 2 ) 707 - 710   2021.02 [ Peer Review Accepted ]

Type of publication: Research paper (other science council materials etc.)

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The treatment duration for candidemia with septic pulmonary embolism should be determined based on the clearance of fungus from the bloodstream and improvement of symptoms. The remaining lung nodules may not necessarily indicate persistent infection.

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ERG3-Encoding Sterol C5,6-DESATURASE in Candida albicans Is Required for Virulence in an Enterically Infected Invasive Candidiasis Mouse Model.

Tatsuro Hirayama, Taiga Miyazaki, Makoto Sumiyoshi, Nobuyuki Ashizawa, Takahiro Takazono, Kazuko Yamamoto, Yoshifumi Imamura, Koichi Izumikawa, Katsunori Yanagihara, Shigeru Kohno, Hiroshi Mukae

Pathogens (Basel, Switzerland)   10 ( 1 )   2020.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Gastrointestinal colonization by Candida species is considered the main source of candidemia. The ERG3 gene in Candida albicans encodes a sterol C5,6-desaturase, which is essential for ergosterol biosynthesis. Although ERG3 inactivation shows reduced virulence in mouse models of disseminated candidiasis, the role of ERG3 in intestinal infections is unknown. Here, we infected mice with the C. albicans strains CAE3DU3 and CAF2-1, containing mutant and wild-type ERG3, respectively, and studied gut infection and colonization by these strains. We found that the CAE3DU3 strain showed reduced colonization, pathogenesis, damage to gut mucosa, and chemokine production in the mouse model of invasive candidiasis. Additionally, mice inoculated with CAE3DU3 showed lower mortality than mice inoculated with CAF2-1 (p < 0.0001). Chemokines were less induced in the gut inoculated with CAE3DU3 than in the gut inoculated with CAF2-1. Histopathologically, although the wild-type gene was associated with a higher pathogenicity and invasion of the gut mucosa and liver tissues causing remarkable tissue necrosis, the erg3/erg3 mutant was associated with a higher accumulation of cells and lower damage to surrounding tissues than wild-type ERG3. These results establish that the ergosterol biosynthetic pathway may be associated with C. albicans gut colonization and subsequent dissemination.

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Diagnostic evaluation of serum (1, 3)-β-d-glucan levels using the Fungitec G-Test MK kit for Pneumocystis jirovecii pneumonia (PCP) in non-HIV patients.

Shuhei Ideguchi, Kazuko Yamamoto, Tatsuro Hirayama, Takahiro Takazono, Yoshifumi Imamura, Taiga Miyazaki, Noriho Sakamoto, Koichi Izumikawa, Katsunori Yanagihara, Shimpei Morimoto, Hiroshi Mukae

Medical mycology     2020.12 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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Pneumocystis jirovecii pneumonia (PCP) is an opportunistic and life-threatening pulmonary infection with an increasing prevalence among individuals who are human immunodeficiency virus (HIV)-negative. Evidence regarding diagnostic testing of PCP in this patient population is insufficient. We evaluated the performance of serum (1, 3)-β-d-glucan (BDG) using the Fungitec G-test MK kit for diagnosing PCP in non-HIV patients. We retrospectively analyzed data from 219 non-HIV adult patients who underwent bronchoscopy and were tested for P. jirovecii DNA by PCR using lavage samples from the lower respiratory tract. Fifty PCP patients and 125 non-PCP patients were included. The most common underlying diseases were malignancies and systemic autoimmune diseases. Using the serum BDG Fungitec G-test MK test to diagnose PCP, the area under the receiver operating characteristic curve (AUC) was 0.924, whereas the modified cut-off value of 36.6 pg/mL had a sensitivity and specificity of 92.0% and 84.8%, respectively. The AUC for patients with systemic autoimmune diseases was 0.873, and the accuracy of serum BDG test declined when using methotrexate (MTX). In conclusion, the serum BDG test was useful for diagnosing PCP in non-HIV patients; however, the results should be carefully interpreted in case of MTX administration. LAY SUMMARY: The Fungitec G-test MK kit for measuring serum (1, 3)-β-d-glucan (BDG) levels had a sufficient diagnostic performance for Pneumocystis jirovecii pneumonia (PCP) in human immunodeficiency virus-negative patients. However, the results should be carefully interpreted in case of MTX administration.

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Influenza A (H3N2) infection followed by anti-signal recognition particle antibody-positive necrotizing myopathy: A case report.

Jun Iriki, Kazuko Yamamoto, Hiroaki Senju, Atsushi Nagaoka, Masataka Yoshida, Keisuke Iwasaki, Nobuyuki Ashizawa, Tatsuro Hirayama, Masato Tashiro, Takahiro Takazono, Yoshifumi Imamura, Taiga Miyazaki, Koichi Izumikawa, Katsunori Yanagihara, Akira Tsujino, Junya Fukuoka, Masataka Uetani, Minoru Satoh, Hiroshi Mukae

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases   103   33 - 36   2020.11 [ Peer Review Accepted ]

Type of publication: Research paper (scientific journal)

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A 60-year-old Japanese woman presented with subacute progressive muscle pain and weakness in her proximal extremities. She was diagnosed with influenza A (H3N2) infection a week before the onset of muscle pain. At the time of admission, she exhibited weakness in the proximal muscles of the upper and lower limbs, elevated serum liver enzymes and creatinine kinase, and myoglobinuria. She did not manifest renal failure and cardiac abnormalities, indicating myocarditis. Electromyography revealed myogenic changes, and magnetic resonance imaging of the upper limb showed abnormal signal intensities in the muscles, suggestive of myopathy. Muscle biopsy of the biceps revealed numerous necrotic regeneration fibers and mild inflammatory cell infiltration, suggesting immune-mediated necrotizing myopathy (IMNM). Necrotized muscle cells were positive for human influenza A (H3N2). Autoantibody analysis showed the presence of antibodies against the signal recognition particle (SRP), and the patient was diagnosed with anti-SRP-associated IMNM. She was resistant to intravenous methylprednisolone pulse therapy but recovered after administration of oral systemic corticosteroids and immunoglobulins. We speculate that the influenza A (H3N2) infection might have triggered her IMNM. Thus, IMNM should be considered as a differential diagnosis in patients with proximal muscle weakness that persists after viral infections.

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