論文 - 宮崎 泰可
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75歳以上のインフルエンザ患者に対するバロキサビル マルボキシルの有効性，安全性：CAPSTONE-2部分集団分析. 査読あり
髙園貴弘、宮崎泰可、吉田祐樹、小嶋悟史、細萱直希、迎 寛
感染症学雑誌 95 ( 1 ) 1 - 8 2022年2月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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A case of Lemierre's syndrome with double vision as the first symptom. 査読あり
Fukushima K, Takazono T, Ashizawa N, Hara S, Kitaoka K, Ideguchi R, Miyazaki T, Hirayama T, Yamamoto K, Imamura Y, Miyazaki T, Izumikawa K, Mukae H.
J Infect Chemother 28 ( 2 ) 286 - 289 2022年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Infection and Chemotherapy
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.
DOI： 10.1016/j.jiac.2021.09.008. Epub 2021 Sep 29. PMID: 34598877.
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Tanida R., Tsubouchi H., Yanagi S., Saito Y., Toshinai K., Miyazaki T., Takamura T., Nakazato M.
Biochemical and Biophysical Research Communications 589 260 - 266 2022年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Biochemical and Biophysical Research Communications
Acute respiratory distress syndrome (ARDS) is a critical illness syndrome characterized by dysregulated pulmonary inflammation. Currently, effective pharmacological treatments for ARDS are unavailable. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor type 1a (GHS-R1a), has a pivotal role in regulating energy metabolism and immunomodulation. The role of endogenous ghrelin in ARDS remains unresolved. Herein, we investigated the role of endogenous ghrelin signaling by using GHS-R1a-null (ghsr−/−) mice and lipopolysaccharide (LPS)-induced ARDS model. Ghsr−/− mice survived longer than controls after LPS-induced lung injury. Ghsr−/− mice showed lower levels of pro-inflammatory cytokines and higher oxygenation levels after lung injury. The peritoneal macrophages isolated from ghsr−/− mice exhibited lower levels of cytokines production and oxygen consumption rate after LPS stimulation. Our results indicated that endogenous ghrelin plays a pivotal role in initiation and continuation in acute inflammatory response in LPS-induced ARDS model by modulating macrophage activity, and highlighted endogenous GHS-R1a signaling in macrophage as a potential therapeutic target in this relentless disease.
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Tashiro M., Obata Y., Takazono T., Ota Y., Wakamura T., Shiozawa Y., Tsuyuki A., Miyazaki T., Nishino T., Izumikawa K.
Renal Failure 44 ( 1 ) 282 - 292 2022年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Renal Failure
Acute kidney injury (AKI) often develops during the administration of liposomal amphotericin B (L-AMB), a broad-spectrum antifungal drug. However, clinical recovery approaches for AKI patients administered L-AMB are not well established. This retrospective analysis used the data obtained from hospitals throughout Japan. AKI was defined as a ≥ 1.5-fold increase within 7 days or ≥0.3 mg/dL increase within 2 days in serum creatinine. AKI recovery was defined as a return to creatinine levels below or equal to those recorded before AKI onset. Ninety patients were assessed for recovery from AKI as per the three stages. The incidence of recovery from AKI regardless of its stage was higher, though not significant, in patients administered ≥10 mL/kg/day fluid for 7 consecutive days from AKI onset (63%) than in those who did not (35%, p = 0.053). However, if limited to AKI stage 1 patients, the former group had a significantly higher incidence of recovery (91%) than the latter group (50%, p = 0.017), even after adjusting for confounding factors (odds ratio: 10.135, 95% confidence interval: 1.148–89.513, p = 0.037). The daily fluid volume administered during the 7 consecutive days from AKI onset positively correlated with the recovery from AKI of all stages (p = 0.043). Daily consecutive fluid infusion from AKI onset may be associated with recovery from stage 1 AKI in patients administered L-AMB, with daily fluid volume positively correlating with the incidence of AKI recovery.
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Ito Y., Takazono T., Koga S., Nakano Y., Ashizawa N., Hirayama T., Tashiro M., Saijo T., Yamamoto K., Imamura Y., Miyazaki T., Yanagihara K., Izumikawa K., Mukae H.
BMC Infectious Diseases 21 ( 1 ) 2021年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：BMC Infectious Diseases
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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Hosogaya N., Miyazaki T., Fukushige Y., Takemori S., Morimoto S., Yamamoto H., Hori M., Kurokawa T., Kawasaki Y., Hanawa M., Fujii Y., Hanaoka H., Iwami S., Watashi K., Yamagoe S., Miyazaki Y., Wakita T., Izumikawa K., Yanagihara K., Mukae H., Kohno S., Yotsuyanagi H., Kato Y., Matsumoto T., Tarumoto N., Shiraishi S., Ishii H., Ohno H., Yatera K., Yamamoto Y., Kakeya H.
Trials 22 ( 1 ) 2021年12月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Trials
Objectives: The aim of this trial is to evaluate the antiviral efficacy, clinical efficacy, and safety of nelfinavir in patients with asymptomatic and mild COVID-19. Trial design: The study is designed as a multicenter, open-label, blinded outcome assessment, parallel group, investigator-initiated, exploratory, randomized (1:1 ratio) controlled clinical trial. Participants: Asymptomatic and mild COVID-19 patients will be enrolled in 10 university and teaching hospitals in Japan. The inclusion and exclusion criteria are as follows: Inclusion criteria:(1)Japanese male or female patients aged ≥ 20 years(2)SARS-CoV-2 detected from a respiratory tract specimen (e.g., nasopharyngeal swab or saliva) using PCR, LAMP, or an antigen test within 3 days before obtaining the informed consent(3)Provide informed consent Exclusion criteria:(1)Symptoms developed ≥ 8 days prior to enrolment(2)SpO2 < 96 % (room air)(3)Any of the following screening criteria:a)ALT or AST ≥ 5 × upper limit of the reference rangeb)Child-Pugh class B or Cc)Serum creatinine ≥ 2 × upper limit of the reference range and creatinine clearance < 30 mL/min(4)Poorly controlled diabetes (random blood glucose ≥ 200 mg/dL or HbA1c ≥ 7.0%, despite treatment)(5)Unsuitable serious complications based on the assessment of either the principal investigator or the sub-investigator(6)Hemophiliac or patients with a marked hemorrhagic tendency(7)Severe diarrhea(8)Hypersensitivity to the investigational drug(9)Breastfeeding or pregnancy(10)With childbearing potential and rejecting contraceptive methods during the study period from the initial administration of the investigational drug(11)Receiving rifampicin within the previous 2 weeks(12)Participated in other clinical trials and received drugs within the previous 12 weeks(13)Undergoing treatment for HIV infection(14)History of SARS-CoV-2 vaccination or wishes to be vaccinated against SARS-CoV-2(15)Deemed inappropriate (for miscellaneous reasons) based on the assessment of either the principal investigator or the sub-investigator Intervention and comparator: Patients who meet the inclusion criteria and do not meet any of the exclusion criteria will be randomized to either the nelfinavir group or the symptomatic treatment group. The nelfinavir group will be administered 750 mg of nelfinavir orally, three times daily for 14 days (treatment period). However, if a participant tests negative on two consecutive PCR tests of saliva samples, administration of the investigational drug for that participant can be discontinued at the discretion of the investigators. The symptomatic treatment group will not be administered the investigational drug, but all other study procedures and conditions will be the same for both groups for the duration of the treatment period. After the treatment period of 14 days, each group will be followed up for 14 days (observational period). Main outcomes: The primary endpoint is the time to negative conversion of SARS-CoV-2. During the study period from Day 1 to Day 28, two consecutive negative PCR results of saliva samples will be considered as the negative conversion of the virus. The secondary efficacy endpoints are as follows: For patients with both asymptomatic and mild disease: area under the curve of viral load, half decay period of viral load, body temperature at each time point, all-cause mortality, incidence rate of pneumonia, percentage of patients with newly developed pneumonia, rate of oxygen administration, and the percentage of patients who require oxygen administration. For asymptomatic patients: incidence of symptomatic COVID-19, incidence of fever (≥ 37.0 °C for two consecutive days), incidence of cough For patients with mild disease: incidence of defervescence (< 37.0 °C), incidence of recovery from clinical symptoms, incidence of improvement of each symptom The secondary safety endpoints are adverse events and clinical examinations. Randomization: Patients will be randomized to either the nelfinavir group or the symptomatic treatment group using the electric data capture system (1:1 ratio, dynamic allocation based on severity [asymptomatic], and age [< 60 years]). Blinding (masking): Only the assessors of the primary outcome will be blinded (blinded outcome assessment). Numbers to be randomized (sample size): The sample size was determined based on our power analysis to reject the null hypothesis, S (t | z =1) = S (t | z = 0) where S is a survival function, t is time to negative conversion, and z denotes randomization group, by the log-rank test with a two-sided p value of 0.05. We estimated viral dynamic parameters by fitting a nonlinear mixed-effects model to reported viral load data, and simulated our primary endpoint from viral-load time-courses that were realized from sets of viral dynamics parameters sampled from the estimated probability distribution of the parameters (sample size: 2000; 1000 each for randomization group). From this estimation of the hazard ratio between the randomization groups for the event of negative conversion using this simulation dataset, the required number of events for rejecting our null hypothesis with a power of 0.80 felled 97.345 by plugging the estimated hazard ratio, 1.79, in Freedman’s equation. Therefore, we decided the required number of randomizations to be 120 after consideration of the frequency of censoring and the anticipated rate of withdrawal caused by factors such as withdrawal of consent. Trial Status: Protocol version 6.0 of February 12, 2021. Recruitment started on July 22, 2020 and is anticipated to be completed by March 31, 2022. Trial registration: This trial was registered in Japan Registry of Clinical Trials (jRCT) (jRCT2071200023) on 21 July 21, 2020. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).
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Irifune S., Ashizawa N., Takazono T., Mutantu P., Nabeshima T., Ngwe Tun M.M., Ota K., Hirayama T., Fujita A., Tashiro M., Tanaka T., Yamamoto K., Imamura Y., Miyazaki T., Sawai T., Izumikawa K., Yanagihara K., Morita K., Mukae H.
Journal of Infection and Chemotherapy 27 ( 10 ) 1525 - 1528 2021年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Infection and Chemotherapy
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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Tashiro M., Takazono T., Ota Y., Wakamura T., Takahashi A., Sato K., Miyazaki T., Obata Y., Nishino T., Izumikawa K.
Journal of Infection and Chemotherapy 27 ( 10 ) 1471 - 1476 2021年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Infection and Chemotherapy
Introduction: Liposomal amphotericin B (L-AMB), a broad spectrum anti-fungicidal drug, is often administered to treat invasive fungal infections (IFIs). However, the most suitable time to initiate treatment in septic shock patients with IFI is unknown. Methods: Patients with septic shock treated with L-AMB were identified from the Japanese Diagnosis Procedure Combination national database and were stratified according to L-AMB treatment initiation either at septic shock onset (early L-AMB group) or after the onset (delayed L-AMB group) to determine their survival rates following septic shock onset and the shock cessation period. Results: We identified 141 patients administered L-AMB on the day of or after septic shock onset: 60 patients received early treatment, whereas 81 patients received delayed treatment. Survival rates after septic shock onset were higher in the early L-AMB group than in the delayed L-AMB group (4 weeks: 68.4% vs 57.9%, P = 0.197; 6 weeks: 62.2% vs 44.5%, P = 0.061; 12 weeks: 43.4% vs 35.0%, P = 0.168, respectively). The septic shock cessation period was shorter in the early L-AMB group than in the delayed L-AMB group (7.0 ± 7.0 days vs 16.5 ± 15.4 days, P < 0.001), with a significant difference confirmed after adjusting for confounding factors with propensity score matching (7.1 ± 7.2 days vs 16.7 ± 14.0 days, P = 0.001). Conclusion: Early L-AMB administration at septic shock onset may be associated with early shock cessation.
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Komeda T., Takazono T., Hosogaya N., Miyazaki T., Ogura E., Iwata S., Miyauchi H., Honda K., Fujiwara M., Ajisawa Y., Watanabe H., Kitanishi Y., Hara K., Mukae H.
Clinical Infectious Diseases 73 ( 5 ) E1181 - E1190 2021年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Clinical Infectious Diseases
Background: Baloxavir marboxil (baloxavir) is a single-dose, oral antiinfluenza drug with a novel mechanism of action. We compared the incidence of hospitalization in patients treated with baloxavir vs neuraminidase inhibitors. Methods: In this retrospective, observational, cohort study, we used real-world patient data extracted from a Japanese health insurance claims database. The enrollment period was 1 October 2018 to 17 April 2019. On day 1, eligible patients (N = 339 007) received baloxavir, oseltamivir, zanamivir, or laninamivir. Baseline characteristics were standardized using the inverse probability of treatment weighting method. The primary end point was the incidence of hospitalization (days 2-14). Secondary end points included antibacterial use, secondary pneumonia, and additional antiinfluenza drug use. Results: Compared with the baloxavir group, the incidence of hospitalization was greater in the oseltamivir group (risk ratio [RR] and 95% confidence interval [CI], 1.41 [1.00-2.00]; risk difference [RD] and 95% CI, 0.06 [.01-.12]) and zanamivir group (RR, 1.85 [1.23-2.78]; RD, 0.11 [.02-.20]). Oseltamivir-treated patients were less likely to require antibacterials than baloxavir-treated patients (RR, 0.87 [.82-.91]). However, oseltamivir-treated patients were more likely to be hospitalized with antibacterials (RR, 1.70 [1.21-2.38]) or antibacterial injection (RR, 1.67 [1.17-2.38]) than baloxavir-treated patients (post hoc analysis). Compared with baloxavir-treated patients, additional antiinfluenza drug use was greater in oseltamivir-, zanamivir-, and laninamivir-treated patients (RR, 1.51 [1.05-2.18], 2.84 [2.04-3.96], and 1.68 [1.35-2.10], respectively). Conclusions: Baloxavir is an efficacious antiinfluenza treatment that may reduce hospitalization compared with oseltamivir and zanamivir.
DOI： 10.1093/cid/ciaa1870
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Infectious pneumonia and lower airway microorganisms in patients with rheumatoid arthritis 査読あり
Ideguchi S., Yamamoto K., Tahara M., Koga T., Ide S., Hirayama T., Takazono T., Imamura Y., Miyazaki T., Sakamoto N., Morimoto S., Izumikawa K., Yanagihara K., Ashizawa K., Aoki T., Kawakami A., Yatera K., Mukae H.
Journal of Clinical Medicine 10 ( 16 ) 2021年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Clinical Medicine
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 under-went 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.
DOI： 10.3390/jcm10163552
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Kaku N., Hashiguchi K., Akamatsu N., Wakigawa F., Matsuda J., Komaru K., Nakao T., Harada Y., Hara A., Uno N., Sakamoto K., Morinaga Y., Kitazaki T., Hasegawa H., Miyazaki T., Fukuda M., Izumikawa K., Mukae H., Yanagihara K.
European Journal of Clinical Microbiology and Infectious Diseases 40 ( 8 ) 1743 - 1748 2021年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：European Journal of Clinical Microbiology and Infectious Diseases
We evaluated a novel transcription-reverse transcription concerted reaction (TRC) assay that can detect influenza A and B within 15 min using nasopharyngeal swab and gargle samples obtained from patients with influenza-like illness, between January and March 2018 and between January and March 2019. Based on the combined RT-PCR and sequencing results, in the nasal swabs, the sensitivity and specificity of TRC for detecting influenza were calculated as 1.000 and 1.000, respectively. In the gargle samples, the sensitivity and specificity of TRC were 0.946 and 1.000, respectively. The TRC assay showed comparable performance to RT-PCR in the detection of influenza viruses.
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One-Year Quality of Life Post-Pneumonia Diagnosis in Japanese Adults 査読あり
Glick H.A., Miyazaki T., Hirano K., Gonzalez E., Jodar L., Gessner B.D., Isturiz R.E., Arguedas A., Kohno S., Suaya J.A.
Clinical Infectious Diseases 73 ( 2 ) 283 - 290 2021年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Clinical Infectious Diseases
Background: Pneumonia is a common, serious illness in the elderly, with a poorly characterized long-term impact on health-related quality of life (HRQoL). The Japanese Goto Epidemiology Study is a prospective, active, population-based surveillance study of adults with X-ray/CT scan-confirmed community-onset pneumonia, assessing the HRQoL outcome quality-adjusted life-years (QALYs). We report QALY scores and losses among a subset of participants in this study. Methods: QALYs were derived from responses to the Japanese version of the EuroQol-5D-5L health-state classification instrument at days 0, 7, 15, 30, 90, 180, and 365 after pneumonia diagnosis from participants enrolled from June 2017 to May 2018. We used patients as their own controls, calculating comparison QALYs by extrapolating EuroQol-5D-5L scores for day -30, accounting for mortality and changes in scores with age. Results: Of 405 participants, 85% were aged ≥65 years, 58% were male, and 69% were hospitalized for clinically and radiologically confirmed pneumonia. Compliance with interviews by patients or proxies was 100%. Adjusted EuroQol-5D-5L scores were 0.759, 0.561, 0.702, and 0.689 at days -30, 0 (diagnosis), 180, and 365, respectively. Average scores at all time points remained below the average day -30 scores (P ≤. 001). Pneumonia resulted in a 1-year adjusted loss of 0.13 QALYs (∼47.5 quality-adjusted days) (P <. 001). Conclusions: Substantial QALY losses were observed among Japanese adults following pneumonia diagnosis, and scores had not returned to prediagnosis levels at 1 year postdiagnosis. QALY scores and cumulative losses were comparable to those in US adults with chronic heart failure, stroke, or renal failure.
DOI： 10.1093/cid/ciaa595
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Evaluation of four commercial severe acute respiratory coronavirus 2 antibody tests. 査読あり
Ashizawa N, Takazono T, Ohyama K, Nagasaki Y, Okamoto M, Hirayama T, Takahashi K, Yamanashi H, Tashiro M, Hosogaya N, Tanaka T, Yamamoto K, Fukuda Y, Imamura Y, Kawanami T, Miyazaki T, Sawai T, Fukushima K, Yatera K, Yanagihara K, Izumikawa K, Mukae H.
J Infect Chemother 27 ( 7 ) 1033 - 1038 2021年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Infection and Chemotherapy
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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Ideguchi S., Yamamoto K., Hirayama T., Takazono T., Imamura Y., Miyazaki T., Sakamoto N., Izumikawa K., Yanagihara K., Morimoto S., Mukae H.
Medical Mycology 59 ( 6 ) 616 - 623 2021年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Medical Mycology
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.
DOI： 10.1093/mmy/myaa101
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Taniguchi H, Takemoto S, Ozasa M, Honda N, Suyama T, Umeyama Y, Dotsu Y, Nakao T, Tomohito K, Gyotoku H, Yamaguchi H, Miyazaki T, Sakamoto N, Obase Y, Fukuda M, Fukuoka J, Mukae H.
Thorac Cancer 12 ( 7 ) 1126 - 1130 2021年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Thoracic Cancer
Pulmonary sarcomatoid carcinoma (SC) is an aggressive subtype of lung cancer that exhibits resistance to cytotoxic chemotherapy. Although programmed cell death 1 (PD-1) inhibitors have been reported to show antitumor effects in patients with high programmed death-ligand 1 (PD-L1) expressing SC, the efficacy of combined therapy with PD-1 inhibitor plus cytotoxic chemotherapy has not previously been clarified. We herein report a case of SC with low expression of PD-L1 and few pre-existing tumor-infiltrating lymphocytes which showed a remarkable response to pembrolizumab plus cytotoxic chemotherapy as first-line treatment. Our findings suggest that combined treatment might enhance the immunogenic response, even in immunologically ignored SCs.
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Ejima K, Kim KS, Iwanami S, Fujita Y, Li M, Zoh RS, Aihara K, Miyazaki T, Wakita T, Iwami S.
J R Soc Interface 18 ( 177 ) 20200947 2021年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of the Royal Society Interface
Viral tests including polymerase chain reaction (PCR) tests are recommended to diagnose COVID-19 infection during the acute phase of infection. A test should have high sensitivity; however, the sensitivity of the PCR test is highly influenced by viral load, which changes over time. Because it is difficult to collect data before the onset of symptoms, the current literature on the sensitivity of the PCR test before symptom onset is limited. In this study, we used a viral dynamics model to track the probability of failing to detect a case of PCR testing over time, including the presymptomatic period. The model was parametrized by using longitudinal viral load data collected from 30 hospitalized patients. The probability of failing to detect a case decreased toward symptom onset, and the lowest probability was observed 2 days after symptom onset and increased afterwards. The probability on the day of symptom onset was 1.0% (95% CI: 0.5 to 1.9) and that 2 days before symptom onset was 60.2% (95% CI: 57.1 to 63.2). Our study suggests that the diagnosis of COVID-19 by PCR testing should be done carefully, especially when the test is performed before or way after symptom onset. Further study is needed of patient groups with potentially different viral dynamics, such as asymptomatic cases.
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Obata Y, Takazono T, Tashiro M, Ota Y, Wakamura T, Takahashi A, Sato K, Miyazaki T, Nishino T, Izumikawa K.
Clin Exp Nephrol 25 ( 3 ) 279 - 287 2021年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Clinical and Experimental Nephrology
Background: Liposomal amphotericin B (L-AMB), a broad-spectrum antifungicidal drug, is often used to treat fungal infections. However, clinical evidence of its use in patients with renal dysfunction, especially those receiving renal replacement therapy (RRT), is limited. Therefore, we evaluated the usage and occurrence of adverse reactions during L-AMB therapy in patients undergoing RRT. Methods: Using claims data and laboratory data, we retrospectively evaluated patients who were administered L-AMB. The presence of comorbidities, mortality rate, treatment with L-AMB and other anti-infective agents, and the incidence of adverse reactions were compared between patients receiving RRT, including continuous renal replacement therapy (CRRT) and maintenance hemodialysis (HD), and those that did not receive RRT. Results: In total, 900 cases met the eligibility criteria: 24, 19, and 842 cases in the maintenance HD, CRRT, and non-RRT groups, respectively. Of the patients administered L-AMB, mortality at discharge was higher for those undergoing either CRRT (15/19; 79%) or maintenance HD (16/24; 67%) than for those not receiving RRT (353/842; 42%). After propensity score matching, the average daily and cumulative dose, treatment duration, and dosing interval for L-AMB were not significantly different between patients receiving and not receiving RRT. L-AMB was used as the first-line antifungal agent for patients undergoing CRRT in most cases (12/19; 63%). Although the number of subjects was limited, the incidence of adverse events did not markedly differ among the groups. Conclusion: L-AMB may be used for patients undergoing maintenance HD or CRRT without any dosing, duration, or interval adjustments.
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Takazono T, Ito Y, Tashiro M, Nakano Y, Hirayama T, Hosogaya N, Saijo T, Yamamoto K, Imamura Y, Miyazaki T, Yanagihara K, Kohno S, Mukae H, Izumikawa K.
J Infect Chemother 27 ( 3 ) 537 - 539 2021年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Infection and Chemotherapy
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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Correction to: The clinical usage of liposomal amphotericin B in patients receiving renal replacement therapy in Japan: a nationwide observational study. 査読あり
Obata Y, Takazono T, Tashiro M, Ota Y, Wakamura T, Takahashi A, Sato K, Miyazaki T, Nishino T, Izumikawa K.
Clin Exp Nephrol 25 ( 3 ) 288 2021年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Iriki J, Yamamoto K, Senju H, Nagaoka A, Yoshida M, Iwasaki K, Ashizawa N, Hirayama T, Tashiro M, Takazono T, Imamura Y, Miyazaki T, Izumikawa K, Yanagihara K, Tsujino A, Fukuoka J, Uetani M, Satoh M, Mukae H.
Int J Infect Dis 103 33 - 36 2021年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Infectious Diseases
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.
DOI： doi:10.1016/j.ijid.2020.11.153. Epub 2020 Nov 18. PMID: 33217572.