論文 - 宮崎 泰可
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Miyazaki T, Hosogaya N, Fukushige Y, Takemori S, Morimoto S, Yamamoto H, Hori M, Ozawa Y, Shiko Y, Inaba Y, Kurokawa T, Hanaoka H, Iwanami S, Kim K, Iwami S, Watashi K, Miyazawa K, Umeyama T, Yamagoe S, Miyazaki Y, Wakita T, Sumiyoshi M, Hirayama T, Izumikawa K, Yanagihara K, Mukae H, Kawasuji H, Yamamoto Y, Tarumoto N, Ishii H, Ohno H, Yatera K, Kakeya H, Kichikawa Y, Kato Y, Matsumoto T, Saito M, Yotsuyanagi H, Kohno S
Microbiology spectrum 11 ( 3 ) e0431122 2023年5月
担当区分：筆頭著者, 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：Microbiology Spectrum
Nelfinavir, an orally administered inhibitor of human immunodeficiency virus protease, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) in vitro. We conducted a randomized controlled trial to evaluate the clinical efficacy and safety of nelfinavir in patients with SARS-CoV-2 infection. We included unvaccinated asymptomatic or mildly symptomatic adult patients who tested positive for SARS-CoV-2 infection within 3 days before enrollment. The patients were randomly assigned (1:1) to receive oral nelfinavir (750 mg; thrice daily for 14 days) combined with standard-of-care or standard-of-care alone. The primary endpoint was the time to viral clearance, confirmed using quantitative reverse-transcription PCR by assessors blinded to the assigned treatment. A total of 123 patients (63 in the nelfinavir group and 60 in the control group) were included. The median time to viral clearance was 8.0 (95% confidence interval [CI], 7.0 to 12.0) days in the nelfinavir group and 8.0 (95% CI, 7.0 to 10.0) days in the control group, with no significant difference between the treatment groups (hazard ratio, 0.815; 95% CI, 0.563 to 1.182; P = 0.1870). Adverse events were reported in 47 (74.6%) and 20 (33.3%) patients in the nelfinavir and control groups, respectively. The most common adverse event in the nelfinavir group was diarrhea (49.2%). Nelfinavir did not reduce the time to viral clearance in this setting. Our findings indicate that nelfinavir should not be recommended in asymptomatic or mildly symptomatic patients infected with SARS-CoV-2. The study is registered with the Japan Registry of Clinical Trials (jRCT2071200023). IMPORTANCE The anti-HIV drug nelfinavir suppresses the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. However, its efficacy in patients with COVID-19 has not been studied. We conducted a multicenter, randomized controlled trial to evaluate the efficacy and safety of orally administered nelfinavir in patients with asymptomatic or mildly symptomatic COVID-19. Compared to standard-of-care alone, nelfinavir (750 mg, thrice daily) did not reduce the time to viral clearance, viral load, or the time to resolution of symptoms. More patients had adverse events in the nelfinavir group than in the control group (74.6% [47/63 patients] versus 33.3% [20/60 patients]). Our clinical study provides evidence that nelfinavir, despite its antiviral effects on SARSCoV-2 in vitro, should not be recommended for the treatment of patients with COVID-19 having no or mild symptoms.
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Nakada-Motokawa N, Miyazaki T, Ueda T, Yamagishi Y, Yamada K, Kawamura H, Kakeya H, Mukae H, Mikamo H, Takesue Y, Kohno S
Mycoses 64 ( 12 ) 1498 - 1507 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：Mycoses
Background: Several severity indexes have been reported for critically ill patients. The Pitt bacteremia score (PBS) is commonly used to predict the risk of mortality in patients with bacteraemia. Objectives: To develop a scoring system for predicting mortality in candidaemia patients. Methods: Medical records at five Japanese tertiary hospitals were reviewed. Factors associated with mortality were analysed using logistic regression modelling. The discriminatory power of scoring models was evaluated by assessing the area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results: In total, 422 candidaemia patients were included. Higher PBS, dialysis and retainment of central venous catheter were independent risk factors for all-cause 30-day mortality. However, among the five PBS components, fever was not associated with mortality; therefore, we developed a modified version of the PBS (mPBS) by replacing fever with dialysis. AUC for PBS and mPBS were 0.74 (95% confidence interval [CI]: 0.68–0.80) and 0.76 (95% CI: 0.71–0.82), respectively. The increase in predictive ability of mPBS for 30-day mortality was statistically significant as assessed by NRI (0.24, 95% CI: 0.01–0.46, p =.04) and IRI (0.04, 95% CI: 0.02–0.06, p =.0008). When patients were stratified by mPBS into low (scores 0–3), moderate (4–7) and high risk (≥8), there were significant differences among the survival curves (p <.0001, log-rank test), and 30-day mortality rates were 13.8% (40/290), 36.8% (28/76) and 69.4% (34/49), respectively. Conclusions: mPBS can be a useful tool for predicting mortality in candidaemia patients.
DOI： 10.1111/myc.13380
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Kim K.S., Iwanami S., Oda T., Fujita Y., Kuba K., Miyazaki T., Ejima K., Iwami S.
Life Science Alliance 4 ( 10 ) 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：Life Science Alliance
The duration of viral shedding is determined by a balance between de novo infection and removal of infected cells. That is, if infection is completely blocked with antiviral drugs (100% inhibition), the duration of viral shedding is minimal and is determined by the length of virus production. However, some mathematical models predict that if infected individuals are treated with antiviral drugs with efficacy below 100%, viral shedding may last longer than without treatment because further de novo infections are driven by entry of the virus into partially protected, uninfected cells at a slower rate. Using a simple mathematical model, we quantified SARS-CoV-2 infection dynamics in non-human primates and characterized the kinetics of viral shedding. We counterintuitively found that treatments initiated early, such as 0.5 d after virus inoculation, with intermediate to relatively high efficacy (30-70% inhibition of virus replication) yield a prolonged duration of viral shedding (by about 6.0 d) compared with no treatment.
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Iwanami S., Ejima K., Su Kim K., Noshita K., Fujita Y., Miyazaki T., Kohno S., Miyazaki Y., Morimoto S., Nakaoka S., Koizumi Y., Asai Y., Aihara K., Watashi K., Thompson R.N., Shibuya K., Fujiu K., Perelson A.S., Iwami S., Wakita T.
PLoS Medicine 18 ( 7 ) 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：PLoS Medicine
Background Development of an effective antiviral drug for Coronavirus Disease 2019 (COVID-19) is a global health priority. Although several candidate drugs have been identified through in vitro and in vivo models, consistent and compelling evidence from clinical studies is limited. The lack of evidence from clinical trials may stem in part from the imperfect design of the trials. We investigated how clinical trials for antivirals need to be designed, especially focusing on the sample size in randomized controlled trials Methods and findings A modeling study was conducted to help understand the reasons behind inconsistent clinical trial findings and to design better clinical trials. We first analyzed longitudinal viral load data for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) without antiviral treatment by use of a within-host virus dynamics model. The fitted viral load was categorized into 3 different groups by a clustering approach. Comparison of the estimated parameters showed that the 3 distinct groups were characterized by different virus decay rates (p-value < 0.001). The mean decay rates were 1.17 d-1 (95% CI: 1.06 to 1.27 d-1), 0.777 d-1 (0.716 to 0.838 d-1), and 0.450 d-1 (0.378 to 0.522 d-1) for the 3 groups, respectively. Such heterogeneity in virus dynamics could be a confounding variable if it is associated with treatment allocation in compassionate use programs (i.e., observational studies). Subsequently, we mimicked randomized controlled trials of antivirals by simulation. An antiviral effect causing a 95% to 99% reduction in viral replication was added to the model. To be realistic, we assumed that randomization and treatment are initiated with some time lag after symptom onset. Using the duration of virus shedding as an outcome, the sample size to detect a statistically significant mean difference between the treatment and placebo groups (1:1 allocation) was 13,603 and 11,670 (when the antiviral effect was 95% and 99%, respectively) per group if all patients are enrolled regardless of timing of randomization. The sample size was reduced to 584 and 458 (when the antiviral effect was 95% and 99%, respectively) if only patients who are treated within 1 day of symptom onset are enrolled. We confirmed the sample size was similarly reduced when using cumulative viral load in log scale as an outcome. We used a conventional virus dynamics model, which may not fully reflect the detailed mechanisms of viral dynamics of SARS-CoV-2. The model needs to be calibrated in terms of both parameter settings and model structure, which would yield more reliable sample size calculation. Conclusions In this study, we found that estimated association in observational studies can be biased due to large heterogeneity in viral dynamics among infected individuals, and statistically significant effect in randomized controlled trials may be difficult to be detected due to small sample size. The sample size can be dramatically reduced by recruiting patients immediately after developing symptoms. We believe this is the first study investigated the study design of clinical trials for antiviral treatment using the viral dynamics model.
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Revisiting the guidelines for ending isolation for covid-19 patients 査読あり
Jeong Y.D., Ejima K., Kim K.S., Iwanami S., Bento A.I., Fujita Y., Jung I.H., Aihara K., Watashi K., Miyazaki T., Wakita T., Iwami S., Ajelli M.
eLife 10 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：eLife
Since the start of the COVID-19 pandemic, two mainstream guidelines for defining when to end the isolation of SARS-CoV-2-infected individuals have been in use: the one-size-fits-all approach (i.e. patients are isolated for a fixed number of days) and the personalized approach (i.e. based on repeated testing of isolated patients). We use a mathematical framework to model within-host viral dynamics and test different criteria for ending isolation. By considering a fixed time of 10 days since symptom onset as the criterion for ending isolation, we estimated that the risk of releasing an individual who is still infectious is low (0–6.6%). However, this policy entails lengthy unnecessary isolations (4.8–8.3 days). In contrast, by using a personalized strategy, similar low risks can be reached with shorter prolonged isolations. The obtained findings provide a scientific rationale for policies on ending the isolation of SARS-CoV-2-infected individuals.
DOI： 10.7554/eLife.69340
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Nabeshima T, Takazono T, Ashizawa N, Miyazaki T, Inoue S, Ngwe Tun MM, Izumikawa K, Mukae H, Moi ML, Morita K.
Lancet Reg Health West Pac 7 100104 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：The Lancet Regional Health - Western Pacific
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Honda M., Tsubouchi H., Inomata R., Yanagi S., Sakai K., Shiomi K., Nakazato M., Miyazaki T.
Peptides 196 2026年3月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Peptides
Sarcopenia is a progressive and generalized skeletal muscle disorder characterized by reduced muscle mass and strength, leading to adverse outcomes such as frailty and increased mortality. Pneumonia can accelerate the progression of sarcopenia, particularly in older adults, by promoting systemic inflammation, reducing physical activity, and impairing respiratory and swallowing muscle function. No effective therapeutic interventions for sarcopenia have been established. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), is produced primarily in the stomach and is known to stimulate appetite, suppress inflammation, and prevent muscle catabolism. Here, we showed that intraperitoneal ghrelin given every 12 h attenuated skeletal-muscle atrophy in aged mice with lipopolysaccharide (LPS)-induced lung injury. Ghrelin treatment preserved muscle weight and mass, suppressed the FoxO1-dependent expression of muscle-specific E3 ubiquitin ligases, muscle RING-finger protein-1, and F-Box protein 32 in the gastrocnemius muscle, and improved the muscle contractile force and voluntary wheel-running activity. In parallel, ghrelin treatment attenuated histological lung injury and was associated with lower levels of inflammatory cytokines in bronchoalveolar lavage fluid. In vitro, ghrelin treatment of LPS-stimulated C2C12 myotubes suppressed reactive oxygen species accumulation and increased the expression of redox-regulating genes including peroxisome proliferator-activated receptor gamma coactivator 1-α and superoxide dismutase 2. Ghrelin also downregulated the LPS-induced expression of muscle-specific ubiquitin ligases in C2C12 cells. These findings suggest that ghrelin has a protective role against inflammation-associated skeletal-muscle atrophy and may have potential as a therapeutic agent for respiratory sarcopenia in the elderly.
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Clinical features of Mycobacterium abscessus complex and Mycobacterium kansasii pulmonary disease in Kyushu, Japan. 査読あり
Takeda K, Takazono T, Ide S, Yoshida M, Iwanaga N, Hosogaya N, Tsukamoto Y, Irifune S, Suyama T, Umemura A, Mihara T, Kondo A, Kobayashi T, Sasaki E, Sawai T, Higashiyama Y, Hashiguchi K, Hanaka M, Ii T, Fukushima K, Komiya K, Miyazaki T, Yatera K, Izumikawa K, Furumoto A, Yanagihara K, Mukae H.
Respir Investig. 64 ( 1 ) 101358. 2026年1月
掲載種別：研究論文（学術雑誌）
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Stratification of viral shedding patterns in saliva of COVID-19 patients. 査読あり
Park H, Raiki Y, Iwanami S, Kim K, Ejima K, Nakamura N, Aihara K, Miyazaki Y, Umeyama T, Miyazawa K, Morita T, Watashi K, Brooke CB, Ke R, Iwami S, Miyazaki T.
Elife. 13 RP96032. 2026年1月
掲載種別：研究論文（学術雑誌）
DOI： 10.7554/eLife.96032.
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"Upper Limb Ataxia Among Residents With Chronic Inorganic Arsenic Exposure: A Quantitative Pilot Study. " 査読あり
Sato Y, Ishii N, Sugiyama T, Shiomi K, Miyazaki T, Mochizuki H
Cureus 2025年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Miyazaki T., Shimamura S., Nagayoshi Y., Nakayama H., Morita A., Tanaka Y., Matsumoto Y., Inamine T., Nishikawa H., Nakada N., Sumiyoshi M., Hirayama T., Kohno S., Mukae H.
Nature Communications 16 ( 1 ) 1023 2025年12月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Nature Communications
Multidrug resistance in the pathogenic fungus Candida glabrata is a growing global threat. Here, we study mechanisms of multidrug resistance in this pathogen. Exposure of C. glabrata cells to micafungin (an echinocandin) leads to the isolation of a mutant exhibiting resistance to echinocandin and azole antifungals. The drug-resistant phenotype is due to a non-synonymous mutation (R70H) in gene IPI1, which is involved in pre-rRNA processing. Azole resistance in the ipi1R70H mutant depends on the Pdr1 transcription factor, which regulates the expression of multidrug transporters. The C. glabrata Ipi1 protein physically interacts with the ribosome-related chaperones Ssb and Ssz1, both of which bind to Pdr1. The Ipi1-Ssb/Ssz1 complex inhibits Pdr1-mediated gene expression and multidrug resistance in C. glabrata, in contrast to Saccharomyces cerevisiae where Ssz1 acts as a positive regulator of Pdr1. Furthermore, micafungin exposure reduces metabolic activity and cell proliferation in the ipi1R70H mutant, which may contribute to micafungin tolerance.
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Response to Letter to the Editor: Efficacy and Safety of Nintedanib in Japanese Patients With Early-Stage Idiopathic Pulmonary Fibrosis: A One-Year Interim Analysis From a Multicenter Observational Study in Kyushu and Okinawa, Japan. 査読あり
Sakamoto N, Okamoto M, Tobino K, Ichiyasu H, Ichikado K, Ishii H, Hamada N, Yatera K, Miyazaki T, Ishimoto H, Kido T, Miyramura T, Morimoto S, Hosogaya N, Mukae H.
Clin Ther. 8 S0149-2918(25)00351-0. 2025年11月
掲載種別：研究論文（学術雑誌）
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呼吸器感染症の動向と外来診療の実践的アプローチ
宮崎泰可
日本内科学会雑誌 114 ( 11 ) 2053 - 2055 2025年11月
掲載種別：論文集(書籍)内論文
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Response to Letter to the Editor: Efficacy and Safety of Nintedanib in Japanese Patients With Early-Stage Idiopathic Pulmonary Fibrosis: A One-Year Interim Analysis From a Multicenter Observational Study in Kyushu and Okinawa, Japan. 査読あり
Sakamoto N, Okamoto M, Tobino K, Ichiyasu H, Ichikado K, Ishii H, Hamada N, Yatera K, Miyazaki T, Ishimoto H, Kido T, Miyramura T, Morimoto S, Hosogaya N, Mukae H.
Clin Ther. 8 S0149-2918(25)00351-0. 2025年11月
掲載種別：研究論文（学術雑誌）
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MRSA早期診断のための遺伝子検査の活用
力武雄幹、宮崎泰可
感染症対策ICTジャーナル 20 ( 4 ) 271 - 275 2025年10月
掲載種別：論文集(書籍)内論文
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OMT-28, a synthetic analog of 17,18-epoxyeicosatetraenoic acid, mitigates lipopolysaccharide-induced lung injury in mice. 査読あり
Tsubouchi H, Inomata R, Yanagi S, Honda M, Sakai K, Konkel A, Lossie J, Schunck WH, Nakazato M, Miyazaki T.
Eur J Pharmacol. 10 1007:178238. 2025年10月
掲載種別：研究論文（学術雑誌）
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Cerebral radiation necrosis successfully treated with high-dose bevacizumab. 査読あり
Kugimiya K, Tsubouchi H, Saito K, Kadota Y, Azuma M, Sakai K, Oda Y, Sumiyoshi M, Yanagi S, Miyazaki T.
Respir Med Case Rep. 58 102282. 2025年9月
掲載種別：症例報告
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Multicentre retrospective observational study for development and validation of MAC prognostic score model. 査読あり
Takeda K, Takazono T, Ide S, Yoshida M, Iwanaga N, Hosogaya N, Tsukamoto Y, Irifune S, Suyama T, Mihara T, Kondo A, Kobayashi T, Fukuda Y, Sasaki E, Sawai T, Higashiyama Y, Hashiguchi K, Hanaka M, Ii T, Fukushima K, Komiya K, Miyazaki T, Yatera K, Izumikawa K, Furumoto A, Yanagihara K, Mukae H.
Sci Rep. 15 ( 1 ) 28539 2025年8月
掲載種別：研究論文（学術雑誌）
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Efficacy and Safety of Nintedanib in Japanese Patients With Early-Stage Idiopathic Pulmonary Fibrosis: A One-Year Interim Analysis from a Multicenter Observational Study in Kyushu and Okinawa, Japan. 査読あり
Sakamoto N, Okamoto M, Tobino K, Ichiyasu H, Ichikado K, Ishii H, Hamada N, Yatera K, Miyazaki T, Ishimoto H, Kido T, Miyramura T, Morimoto S, Hosogaya N, Mukae H.
Clin Ther. 47 ( 8 ) 587 - 597 2025年8月
掲載種別：研究論文（学術雑誌）
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Risk Factors and Long-Term Prognosis for Coinfection of Nontuberculous Mycobacterial Pulmonary Disease and Chronic Pulmonary Aspergillosis: A Multicentre Observational Study in Japan. 査読あり
Tanaka Y, Ide S, Takazono T, Takeda K, Iwanaga N, Yoshida M, Hosogaya N, Tsukamoto Y, Irifune S, Suyama T, Mihara T, Kondo A, Kobayashi T, Fukuda Y, Sasaki E, Sawai T, Higashiyama Y, Hashiguchi K, Hanaka M, Ii T, Fukushima K, Komiya K, Miyazaki T, Yatera K, Izumikawa K, Furumoto A, Yanagihara K, Mukae H.
Mycoses. 68 (6):e70083. 2025年6月
掲載種別：研究論文（学術雑誌）