Authorship：Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.resinv.2024.12.001

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INTRODUCTION: Despite the ongoing efforts to refine treatment durations and methods for patients with chronic pulmonary aspergillosis, the clinical use of antifungal agents remains unclear. This study aimed to describe the treatment practices, trajectories, and prognoses of newly diagnosed patients with chronic pulmonary aspergillosis. METHODS: Data from a longitudinal database from hospitals in Japan was used. The target population included patients who started antifungal treatment following their initial diagnosis of pulmonary aspergillosis, pulmonary aspergilloma, or chronic necrotizing pulmonary aspergillosis between October 2015 and September 2017. We described patient characteristics and treatment practices. RESULTS: Of the 680 patients analyzed, 253 (37.2%), 231 (34.0%), 155 (22.8%), 31 (4.6%), and 10 (1.5%) patients received the initial treatment with voriconazole, itraconazole, micafungin, caspofungin, and liposomal amphotericin B, respectively. Over 50% of the patients initially treated with micafungin or caspofungin switched to azoles within a month. Of the patients treated with antifungal agents, only 46.8% continued treatment for 6 months, indicating a lower retention rate. The overall mortality rate at 1 year was 24.7%. The median treatment duration of initial treatment until switching was 83 days (interquartile range [IQR], 159) for voriconazole and 162 days (IQR, 310) for itraconazole, indicating a significant variation in treatment duration. Notably, 15.7% (76/484) of the patients underwent a treatment switch between voriconazole and itraconazole in the initial azole treatment group. CONCLUSIONS: Our findings highlight the challenges associated with sustaining long-term antifungal treatment.

DOI： 10.1007/s40121-024-01094-y

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.clinbiochem.2024.110865

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BACKGROUND: Azithromycin has favorable effects on critical respiratory diseases owing to its antimicrobial and anti-inflammatory properties. During the early stages of the coronavirus disease 2019 (COVID-19) pandemic, azithromycin was frequently administered before specific treatments were developed. However, the efficacy of this treatment has not been verified. We retrospectively investigated the effects of its intravenous (IV) administration in patients with severe/critical COVID-19 using the National Administrative Database of Japan during the first wave (February-April 2020). METHODS: Patients were categorized based on whether they received IV azithromycin within three days of hospitalization. An overlap weighting method with estimated propensity scores was used to reduce bias. RESULTS: Among the 830 patients with severe/critical COVID-19, 148 (17.8 %) received azithromycin, and 682 (82.2 %) did not. After adjustment, the use of azithromycin was associated with a shorter duration of intensive care unit (ICU) management (-3.48 days, 95 % confidence interval [CI]: 4.59 to -2.38). However, other endpoints, including mortality rate, duration of mechanical ventilation, and duration of hospital stay, did not suggest any associations. Furthermore, of the 115 ICU patients, 27 (23.5 %) were treated with IV azithromycin and 88 (76.5 %) were not. After adjustment, azithromycin was associated with favorable outcomes, including reduced in-hospital mortality (odds ratio [OR], 0.45, 95 % CI: 0.22 to 0.92), 30-day mortality (OR, 0.46, 95 % CI: 0.22 to 0.94), and a shorter duration of ICU management (-2.94 days, 95 % CI: 5.15 to -0.73). CONCLUSION: We verified that IV azithromycin was associated with favorable impact in patients with COVID-19 requiring ICU management.

DOI： 10.1016/j.rmed.2024.107834

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Exophiala dermatitidis is an emerging black fungus that causes pulmonary infections that may be underestimated by conventional culture methods. We encountered one case that initially appeared to be yeast and was misidentified as Rhodotorula spp. using a commercial identification kit. Thus, genetic identification and clinical background investigations were conducted on 46 strains of Rhodotorula spp. The sequences of the internal transcribed spacer and large-subunit RNA genes (D1/D2 regions) of 43 isolates, excluding two environmental isolates and one difficult-to-culture isolate, were determined and genetically identified. Notably, 22 isolates were identified as E. dermatitidis and misidentified as Rhodotorula spp. using the conventional method. Based on the exclusion criteria, the clinical information of 11 patients was retrospectively reviewed. Five cases (definite) had definite exacerbation of pulmonary infections due to E. dermatitidis, and six cases (possible) had undeniable infections. Of the 11 cases of pulmonary infection suggested to be caused by E. dermatitidis, comorbidities included two cases of chronic pulmonary aspergillosis (CPA), three cases of pulmonary non-tuberculous mycobacterial (NTM) infection and one case of pulmonary nocardiosis, suggesting a trend towards simultaneous detection of chronic pulmonary infections. Steroid and immunosuppressive drug use was observed in five cases, and β-D-glucan elevation was observed in three of five definite cases of pulmonary infections due to E. dermatitidis. The possibility of E. dermatitidis infection should be considered when Rhodotorula spp. are isolated from cultures of airway-derived specimens, and, in addition to CPA and NTM, identification of E. dermatitidis may be important in chronic pulmonary infections.

DOI： 10.1111/myc.13804

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Objectives: In the present study, we aimed to clarify the mechanisms by which periodontal pathogens, particularly Prevotella intermedia, induce severe neutrophilic inflammation. In addition, we aimed to test the efficacy of macrolides, which has not been resolved in the neutrophilic inflammation induced by P. intermedia. Methods: NCl-H292 human airway epithelial cells were pre-incubated with clarithromycin for 2 h before incubation with P. intermedia supernatants. Then, C-X-C motif chemokine ligand 8 (CXCL8) transcription and interleukin (IL)-8 production were measured. To elucidate the signaling pathway, mitogen-activated protein kinase inhibitors were added to the cell culture, and the cells were subjected to Western blotting. Results:P. intermedia supernatants promoted CXCL8 transcription and IL-8 production, and the reactions were significantly suppressed by clarithromycin pretreatment. Only trametinib, the selective mitogen-activated extracellular signal-regulated kinase inhibitor, downregulated CXCL8 transcription and IL-8 production. Furthermore, Western blotting revealed that stimulation with P. intermedia supernatants specifically induces extracellular signal-regulated kinases (ERK) 1/2 phosphorylation, which is suppressed by clarithromycin pretreatment. Notably, the interference analysis revealed that ERK3 might be dispensable for IL-8 production under the stimulation of P. intermedia supernatants. Conclusions: Our results provide new insight into the mechanism underlying P. intermedia-induced production of IL-8 from human airway epithelial cells. Furthermore, macrolides might have therapeutic potential in regulating periodontal pathogen-induced neutrophilic inflammation in the lungs.

DOI： 10.3390/antibiotics13090909

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Cryobiopsy use is anticipated to become more common in diagnosing lung diseases. In Japan, inserting a Fogarty catheter through a suction channel above the endotracheal tube's cuff for hemostasis is common practice. However, the rigid nature of the endotracheal tube poses challenges to tracheal intubation using a bronchoscope. The endotracheal tube cuff must be removed to prevent interference during Fogarty catheter insertion. To simplify the procedure and enhance safety, we devised and implemented a method of inserting a hemostatic Fogarty catheter with a suction tube externally attached to a softer endotracheal tube. This study aimed to evaluate the sustainability of this Fogarty catheter insertion method using suction tubes. METHODS: The hemostatic Fogarty catheter insertion method was retrospectively validated. We compared outcomes between 60 patients who underwent the conventional method with a suction channel above the cuff and 50 patients who underwent the novel approach with an externally attached suction tube. RESULTS: The physicians performing bronchoscopy and inserting the Fogarty catheter in the group in which the suction tube was externally attached for Fogarty catheter insertion had little experience. However, the overall bronchoscopy time was shorter; the two groups showed no significant differences in complications. CONCLUSION: Regarding cryobiopsy procedures, using an externally attached suction tube for Fogarty catheter insertion was practical and comparable to the conventional method of using a suction channel above the cuff. This method made the procedure more simple and safe.

DOI： 10.1016/j.resinv.2024.06.001

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UNLABELLED: Invasive aspergillosis (IA) and mucormycosis are life-threatening diseases, especially among immunocompromised patients. Drug-resistant Aspergillus fumigatus strains have been isolated worldwide, which can pose a serious clinical problem. As IA mainly occurs in patients with compromised immune systems, the ideal therapeutic approach should aim to bolster the immune system. In this study, we focused on Vγ9Vδ2 T cells that exhibit immune effector functions and examined the possibility of harnessing this unconventional T cell subset as a novel therapeutic modality for IA. A potent antifungal effect was observed when A. fumigatus (Af293) hyphae were challenged by Vγ9Vδ2 T cells derived from peripheral blood. In addition, Vγ9Vδ2 T cells exhibited antifungal activity against hyphae of all Aspergillus spp., Cunninghamella bertholletiae, and Rhizopus microsporus but not against their conidia. Furthermore, Vγ9Vδ2 T cells also exhibited antifungal activity against azole-resistant A. fumigatus, indicating that Vγ9Vδ2 T cells could be used for treating drug-resistant A. fumigatus. The antifungal activity of Vγ9Vδ2 T cells depended on cell-to-cell contact with A. fumigatus hyphae, and degranulation characterized by CD107a mobilization seems essential for this activity against A. fumigatus. Vγ9Vδ2 T cells could be developed as a novel modality for treating IA or mucormycosis. IMPORTANCE: Invasive aspergillosis (IA) and mucormycosis are often resistant to treatment with conventional antifungal agents and have a high mortality rate. Additionally, effective antifungal treatment is hindered by drug toxicity, given that both fungal and human cells are eukaryotic, and antifungal agents are also likely to act on human cells, resulting in adverse effects. Therefore, the development of novel therapeutic agents specifically targeting fungi is challenging. This study demonstrated the antifungal activity of Vγ9Vδ2 T cells against various Aspergillus spp. and several Mucorales in vitro and discussed the mechanism underlying their antifungal activity. We indicate that adoptive immunotherapy using Vγ9Vδ2 T cells may offer a new therapeutic approach to IA.

DOI： 10.1128/spectrum.03614-23

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BACKGROUND: Evidence regarding the association of the usage of biologic agents (Etanercept, Tocilizumab, adalimumab and so on), such as anti-tumor necrosis factor α, with the incidence and risk factors of non-tuberculous Mycobacteria (NTM) infection is limited. Therefore, this study aimed to investigate the incidence and risk factors of NTM and their associations with biologic agents' usage, and also investigated the potential of Mycobacterium avium complex (MAC) antibodies as a predictor of NTM infection development. METHODS: This retrospective study included 672 patients with autoimmune diseases from four hospitals in Nagasaki, Japan, from January 1, 2011, to June 30, 2019, who fulfilled the inclusion criteria. RESULTS: Of the 672 patients, 9 (1.3%) developed complicated NTM infection, including two with disseminated infection, after the introduction of biologic agents. Of the nine patients, two died due to NTM infection but none tested positive for MAC antibodies prior to initiation of biologic agents. The mortality rate was higher in patients complicated with NTM than without NTM (22.2% vs 2.6%, P = 0.024). The corticosteroids dosage at the time of initiating the biologic agents was significantly higher in the NTM group than in the non-NTM group (median, 17 mg vs 3 mg, P = 0.0038). CONCLUSION: In the patients undergoing therapy with biologic agents, although NTM complication was rare, it could be fatal. In particular, for patients on a relatively high dose corticosteroids, careful observation is essential for identifying NTM complication, even if the MAC antibody test is negative.

DOI： 10.1016/j.resinv.2024.02.005

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This retrospective observational study aimed to assess the clinical characteristics of platypnea-orthodeoxia syndrome in patients with coronavirus disease 2019 (COVID-19) treated using mechanical ventilation or high-flow nasal canula. We analyzed 42 consecutive patients with COVID-19 from January 2020 to March 2022. The primary outcomes were the incidence of platypnea-orthodeoxia syndrome, the time with required long-term oxygen therapy, and short-term prognosis. Additionally, we examined the relationships between platypnea-orthodeoxia syndrome and COVID-19 severity, the time with long-term oxygen therapy, and short-term prognosis. Of the 42 included patients, 15 (35.7 %) had platypnea-orthodeoxia syndrome. Although mortality was not significantly different between both groups, the oxygen withdrawal rate in the platypnea-orthodeoxia syndrome group was significantly lower than that in the group without this syndrome. Clinical staff should be aware of the possibility of platypnea-orthodeoxia syndrome during positional changes in patients with COVID-19. Recognizing POS can improve early detection, countermeasures, and safety during physiotherapy.

DOI： 10.1016/j.resinv.2024.01.006

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

This study investigated the utility of periostin, a matricellular protein, as a prognostic biomarker in patients with idiopathic pulmonary fibrosis (IPF) who received nintedanib. Monomeric and total periostin levels were measured by enzyme-linked immunosorbent assay in 87 eligible patients who participated in a multicenter prospective study. Forty-three antifibrotic drug-naive patients with IPF described in previous studies were set as historical controls. Monomeric and total periostin levels were not significantly associated with the change in forced vital capacity (FVC) or diffusing capacity of the lungs for carbon monoxide (D_LCO) during any follow-up period. Higher monomeric and total periostin levels were independent risk factors for overall survival in the Cox proportional hazard model. In the analysis of nintedanib effectiveness, higher binarized monomeric periostin levels were associated with more favorable suppressive effects on decreased vital capacity (VC) and D_LCO in the treatment group compared with historical controls. Higher binarized levels of total periostin were associated with more favorable suppressive effects on decreased D_LCO but not VC. In conclusion, higher periostin levels were independently associated with survival and better therapeutic effectiveness in patients with IPF treated with nintedanib. Periostin assessments may contribute to determining therapeutic strategies for patients with IPF.

DOI： 10.1038/s41598-023-49180-4

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Other Link： https://www.nature.com/articles/s41598-023-49180-4

Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/jcm12227100

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BACKGROUND AND OBJECTIVE: Interstitial lung disease (ILD) encompasses several diverse pulmonary pathologies that result in abnormal diffuse parenchymal changes. When prescribing rehabilitation, several additional factors need to be considered as a result of aging, polypharmacy, and comorbidities manifested in ILD patients. This review aims to discuss issues related to frailty, skeletal muscle and cognitive function that limit physical activities in ILD patients. It will also highlight exercise training and propose complementary strategies for pulmonary rehabilitation. METHODS: A literature search was performed in MEDLINE, CINAHL (inception to October 19th, 2022) using search terms based on concepts of: idiopathic pulmonary fibrosis or interstitial lung disease; frailty; muscular atrophy; skeletal muscle dysfunction; cognitive dysfunction; sleep quality; sleep disorders; anxiety disorders; or depressive disorders. After eligible texts were screened, additional references were included from references cited in the screened articles. KEY CONTENT AND FINDINGS: Frailty and skeletal muscle dysfunction are common in ILD. Weight loss, exhaustion, and anti-fibrotic medications can impact frailty, whereas physical inactivity, aging, corticosteroids and hypoxemia can contribute to sarcopenia (loss of muscle mass and function). Frailty is associated with worse clinical status, exercise intolerance, skeletal muscle dysfunction, and decreased quality of life in ILD. Sarcopenia appears to influence wellbeing and can potentially affect overall physical conditioning, cognitive function and the progression of ILD. Optimal assessment tools and effective strategies to prevent and counter frailty and sarcopenia need to be determined in ILD patients. Even though cognitive impairment is evident in ILD, its prevalence and underlying neurobiological model of contributing factors (i.e., inflammation, disease severity, cardiopulmonary status) requires further investigation. How ILD affects cognitive interference, motor control and consequently physical daily activities is not well defined. Strategies such as pulmonary rehabilitation, which primarily focuses on strength and aerobic conditioning have demonstrated improvements in ILD patient outcomes. Future incorporation of interval training and the integration of motor learning could improve transfer of rehabilitation strategies to daily activities. CONCLUSIONS: Numerous underlying etiologies of ILD contribute to frailty, skeletal muscle and cognitive function, but their respective neurobiologic mechanisms require further investigation. Exercise training increases physical measures, but complementary approaches may improve their applicability to improve daily activities.

DOI： 10.21037/jtd-23-209

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by a progressive decline in lung function and poor prognosis. The deposition of the extracellular matrix (ECM) by myofibroblasts contributes to the stiffening of lung tissue and impaired oxygen exchange in IPF. Type I collagen is the major ECM component and predominant collagen protein deposited in chronic fibrosis, suggesting that type I collagen could be a target of drugs for fibrosis treatment. Heat shock protein 47 (HSP47), encoded by the serpin peptidase inhibitor clade H, member 1 gene, is a stress-inducible collagen-binding protein. It is an endoplasmic reticulum-resident molecular chaperone essential for the correct folding of procollagen. HSP47 expression is increased in cellular and animal models of pulmonary fibrosis and correlates with pathological manifestations in human interstitial lung diseases. Various factors affect HSP47 expression directly or indirectly in pulmonary fibrosis models. Overall, understanding the relationship between HSP47 expression and pulmonary fibrosis may contribute to the development of novel therapeutic strategies.

DOI： 10.3390/biomedicines11092387

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Studies indicated potential harm from empirical broad-spectrum therapy. A recent study of hospitalizations for community-acquired pneumonia suggested that empirical anti-methicillin-resistant Staphylococcus aureus (MRSA) therapy was associated with an increased risk of death and other complications. However, limited evidence supports empirical anti-MRSA therapy for older patients with aspiration pneumonia. In a nationwide Japanese database, patients aged ≥65 years on admission with aspiration pneumonia were analyzed. Patients were divided based on presence of respiratory failure and further sub-categorized based on their condition within 3 days of hospital admission, either receiving a combination of anti-MRSA agents and other antibiotics, or not using MRSA agents. An inverse probability weighting method with estimated propensity scores was used. Out of 81,306 eligible patients, 55,098 had respiratory failure, and 26,208 did not. In the group with and without respiratory failure, 0.93% and 0.42% of the patients, respectively, received anti-MRSA agents. In patients with respiratory failure, in-hospital mortality (31.38% vs. 19.03%, p < 0.001), 30-day mortality, and 90-day mortality were significantly higher, and oxygen administration length was significantly longer in the anti-MRSA agent combination group. Anti-MRSA agent combination use did not improve the outcomes in older patients with aspiration pneumonia and respiratory failure, and should be carefully and comprehensively considered.

DOI： 10.3390/microorganisms11081905

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

This study aimed to examine the validity of urinary N-terminal titin fragment/creatinine (urinary N-titin/Cr) reflecting muscle damage biomarker in patients with interstitial lung disease. This retrospective study enrolled patients with interstitial lung disease. We measured urinary N-titin/Cr. Furthermore, we measured the cross-sectional areas of the pectoralis muscles above the aortic arch (PM_CSA) and erector spinae muscles of the 12th thoracic vertebra muscles (ESM_CSA) to assess muscle mass until 1 year. We examined the correlation between urinary N-titin/Cr and the change in muscle mass. We plotted receiver operating characteristic curves to estimate the cut-off points for urinary N-titin/Cr for distinguishing the greater-than-median and smaller-than-median reduction of muscle mass after 1 year. We enrolled 68 patients with interstitial lung disease. The median urinary N-titin/Cr value was 7.0 pmol/mg/dL. We observed significant negative correlations between urinary N-titin/Cr and changes in the PM_CSA after 1 year (p < 0.001) and changes in the ESM_CSA after 6 months (p < 0.001) and 1 year (p < 0.001). The cut-off points for urinary N-titin/Cr were 5.2 pmol/mg/dL and 10.4 pmol/mg/dL in the PM_CSA and ESM_CSA, respectively. In summary, urinary N-titin/Cr may predict muscle loss in the long-term and act as a clinically useful biomarker reflecting muscle damage.

DOI： 10.1038/s41598-023-36827-5

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Other Link： https://www.nature.com/articles/s41598-023-36827-5

Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/v15051142

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BACKGROUND: Thymic epithelial tumors (TETs) are prone to developing in East Asian populations. However, little is known about the genomic profile of TETs in East Asian populations, and the genomic aberrations in TETs have not yet been fully clarified. Thus, molecular targeted therapies for patients with TETs have not been established. This prospective study was conducted to explore the genetic abnormalities of surgically resected TETs in a Japanese cohort and to identify clues for carcinogenesis and potential therapeutic targets in TETs. METHODS: Genetic profiles of TETs were investigated using fresh-frozen specimens resected from operable cases with TETs. DNA sequencing was performed using a next-generation sequencing (NGS) gene panel test with Ion Reporter™ and CLC Genomics Workbench 11.0. The mutation sites were further confirmed by Sanger sequencing, digital droplet polymerase chain reaction (ddPCR), and TA cloning for validation. RESULTS: Among 43 patients diagnosed with anterior mediastinal tumors between January 2013 and March 2019, NGS and validation analyses were performed in 31 patients [29 thymomas and two thymic cancers (TCs)] who met the study criteria. Of these, 12 cases of thymoma types A, AB, B1, and B2 harbored the general transcription factor 2-I (GTF2I) mutation (L424H). Conversely, the mutation was not detected in type B3 thymoma or TC, suggesting that the GTF2I mutation existed in indolent types of TETs. Rat sarcoma viral oncogene (RAS) mutations were detected in three cases [Harvey RAS (HRAS) in two cases of type AB thymoma and neuroblastoma RAS (NRAS)] in one case of type B1 thymoma), and additional sex combs like 1 (ASXL1) mutation was present in one case of TC. All RAS mutations were observed in GTF2I-mutated cases. CONCLUSIONS: The GTF2I mutation (L424H) is the most frequently occurring mutation in the limited histology of thymoma, consistent with those in the non-Asian population. HRAS and NRAS mutations co-occurred in cases harboring the GTF2I mutation. These findings suggest that the existence of the GTF2I mutation might be related to indolent types of TETs, and RAS mutations could be candidates as therapeutic targets in TETs.

DOI： 10.21037/tlcr-22-794

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BACKGROUND: Interstitial lung disease is frequently comorbid with dermatomyositis and has a poor prognosis, especially in patients with the anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody. However, the pathogenesis of dermatomyositis-related interstitial lung disease remains unclear. METHODS: We examined 18 and 19 patients with dermatomyositis-related interstitial lung disease and idiopathic pulmonary fibrosis (control), respectively. Lung tissues obtained from these patients were semi-quantitatively evaluated by immunohistochemical staining with in-house anti-human MDA5 monoclonal antibodies, as well as anti-human immunoglobulin (Ig) G, IgM, IgA, and complement component 3(C3) antibodies. We established human MDA5 transgenic mice and treated them with rabbit anti-human MDA5 polyclonal antibodies, and evaluated lung injury and Ig and C3 expression. RESULTS: MDA5 was moderately or strongly expressed in the lungs of patients in both groups, with no significant differences between the groups. However, patients with dermatomyositis-related interstitial lung disease showed significantly stronger expression of C3 (p < 0.001), IgG (p < 0.001), and IgM (p = 0.001) in the lungs than control. Moreover, lung C3, but IgG, IgA, nor IgM expression was significantly stronger in MDA5 autoantibody-positive dermatomyositis-related interstitial lung disease (n = 9) than in MDA5 autoantibody-negative dermatomyositis-related interstitial lung disease (n = 9; p = 0.022). Treatment with anti-MDA5 antibodies induced lung injury in MDA5 transgenic mice, and strong immunoglobulin and C3 expression was observed in the lungs of the mice. CONCLUSION: Strong immunoglobulin and C3 expression in the lungs involve lung injury related to dermatomyositis-related interstitial lung disease. Enhanced immune complex formation in the lungs may contribute to the poor prognosis of MDA5 autoantibody-positive dermatomyositis-related interstitial lung disease.

DOI： 10.1186/s12931-023-02362-0

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Primary ciliary dyskinesia (PCD) is a genetic and congenital disease associated with an abnormal ciliary ultrastructure and function and is estimated to affect 1 in 15,000-20,000 individuals. A PCD diagnosis can be achieved by genotyping. Here, we performed whole-exome analysis for the diagnosis of PCD and described the detailed clinical characteristics of the case. A 39-year-old Japanese woman with sinusitis and bronchiectasis without situs inversus had had upper and lower respiratory symptoms since childhood and had received long-term macrolide therapy without an accurate diagnosis. A moderate deterioration of cilia function was observed by high-speed video microscopy analysis; additionally, the number of cells with moving cilia was fewer than that in patients without PCD. Electron microscopy revealed no apparent structural abnormalities. We performed whole-exome analysis and identified novel biallelic variants of SPEF2 in the homozygous state (c.1860_1861insCT). We confirmed the absence of SPEF2 protein expression in the cilia of the nasal mucosa using fluorescent immunostaining. Accordingly, she was diagnosed as having PCD with the SPEF2 variant. The present case suggests that the deterioration of cilia function is moderate, the number of respiratory cells with moving cilia might be reduced, and the respiratory condition could be severe in patients with PCD with the SPEF2 variant.

DOI： 10.3390/jcm12010317

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Diabetes is known to delay wound healing, and this delay is attributed to prolonged inflammation. We found that microRNAs (miRNAs) might be involved in the dysfunction of diabetic-derived neutrophils, and dynamics of neutrophil and chronic inflammation might be initiated by miRNA-regulated genes. Moreover, studies of miRNA function in nephropathy have suggested that circular RNAs (circRNAs), which function as sponges of miRNA to regulate their expression, are potential biomarkers and new therapeutic targets for the diagnosis of diabetic nephropathy. Accordingly, to investigate the molecular mechanism of the regulation of inflammation in diabetic-derived neutrophils, we identified circRNAs in diabetic-derived neutrophils obtained from BKS.Cg-Dock7m +/+ Leprdb/J (Leprdb/db and Leprdb/+) mice using microarrays. Neutrophils from pooled bone marrow of three diabetic and three non-diabetic mice were isolated and total RNA was extracted. Microarray analysis was performed using the Arraystar Mouse Circular RNA Array. The results showed that three circRNAs were significantly increased and six circRNAs were significantly decreased in diabetic-derived neutrophils compared with non-diabetic-derived neutrophils. The expressions of some circRNAs in diabetic-derived neutrophils were more than double those in non-diabetic-derived neutrophils. The circRNAs contain binding sites of miRNAs, which were differentially expressed in diabetic-derived neutrophils. Our results suggest that circRNAs may be involved in the regulation of inflammation in diabetic-derived neutrophils.

DOI： 10.3390/biomedicines10123129

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Authorship：Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Idiopathic pulmonary fibrosis is a chronic intractable lung disease, leading to respiratory failure and death. Although anti-fibrotic agents delay disease progression, they are not considered curative treatments, and alternative modalities have attracted attention. We examined the effect of human γδ T cells on collagen type I in lung fibroblasts. Collagen type I was markedly reduced in a γδ T cell number-dependent manner following treatment with γδ T cells expanded with tetrakis-pivaloxymethyl 2-(thiazole-2-ylamino) ethylidene-1,1-bisphosphonate (PTA) and interleukin-2. Collagen type I levels remained unchanged on addition of γδ T cells to the culture system through a trans-well culture membrane, suggesting that cell–cell contact is essential for reducing its levels in lung fibroblasts. Re-stimulating γδ T cells with (E)-4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP) reduced collagen type I levels without cell–cell contact, indicating the existence of HMBPP-induced soluble anti-fibrotic factors in γδ T cells. Adding anti-interferon-γ (IFN-γ)-neutralizing mAb restored collagen type I levels, demonstrating that human γδ T cell-derived IFN-γ reduces collagen type I levels. Conversely, interleukin-18 augmented γδ T cell-induced suppression of collagen type I. Therefore, human γδ T cells reduce collagen levels in lung fibroblasts via two distinct mechanisms; adoptive γδ T cell transfer is potentially a new therapeutic candidate.

DOI： 10.3390/cells11182816

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/jcm11185444

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Antibodies to Ro52/tripartite motif-containing 21 (TRIM21), referred to as anti-Ro52, are found in patients diagnosed with diverse systemic autoimmune rheumatic disease and associated with interstitial lung diseases. However, little is known about the clinical characteristics of anti-Ro52 in patients with idiopathic interstitial pneumonias (IIPs). We aimed to analyze the prevalence, co-existent autoantibodies, and clinical characteristics of anti-Ro52 in patients with IIP. The study enrolled 288 patients diagnosed with IIP. Clinical, laboratory and radiographic findings of IIP patients were compared between anti-Ro52 positives and negatives. Anti-Ro52 (20/288; 6.9%), anti-ARS (18/288; 6.3%), and anti-Ro60/SS-A (16/288; 5.6%) were the most common autoantibodies detected in IIP patients. Among 20 IIP patients who had anti-Ro52, anti-ARS was present in 8 (40%) patients. The criteria for interstitial pneumonia with autoimmune features (IPAF) were significantly better fulfilled by patients with anti-Ro52 than those without (P = 0.001). Meeting serological domain (P < 0.001) and Raynaud's phenomenon (P = 0.009) were significantly more common in the anti-Ro52-positive patients. Anti-Ro52-positive IIP patients have clinical features consistent with IPAF. Anti-Ro52 may have an important role in detecting the autoimmune phenotype in IIP patients.

DOI： 10.1038/s41598-022-15321-4

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

A 26-year-old Japanese woman was admitted with a 1-month history of diarrhea, a high fever for a few days, and exacerbation of dyspnea. She was treated with an antifibrotic drug and long-term oxygen therapy for Hermansky-Pudlak syndrome-related pulmonary fibrosis. New ground-glass attenuation appeared on chest computed tomography (CT), and a colon biopsy showed an inflammatory cell accumulation with a high titer of myeloperoxidase (MPO)-specific anti-neutrophil cytoplasmic antibodies (ANCA). Systemic inflammation related to MPO-ANCA titer elevation was suspected. Steroid pulse therapy and intravenous cyclophosphamide improved chest CT findings and diarrhea. Therefore, immunosuppressant treatment should be considered for systemic inflammation related to MPO-ANCA.

DOI： 10.2169/internalmedicine.9350-22

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DOI： 10.3390/v14020279

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DOI： 10.1016/j.pulmoe.2021.07.003

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DOI： 10.1186/s12890-022-01840-3

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-021-02861-4

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s12931-021-01671-6

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.rmed.2021.106612

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: to evaluate the number of cases of idiopathic pulmonary fibrosis (IPF) that included histological features of connective tissue disease (CTD) and to check whether they demonstrated the clinical features of CTD, using a previously reported CTD-interstitial pneumonia (IP) index that histologically differentiates CTD-associated and idiopathic IP. METHODS: patients diagnosed with IPF following video-assisted thoracoscopic biopsy through multidisciplinary team diagnosis between 2014 and 2017 were selected. Pathological observation was made by four pathologists who scored eight observational items needed for the CTD-IP index. Cases determined as CTD, by the CTD-IP index, were extracted, and their clinical features were compared. RESULTS: a total of 94 cases of IPF were identified, of which 20 were classified into the CTD group using the CTD-IP index with reasonable interobserver agreement (k = 0.76). Cases pathologically classified into the CTD group were significantly associated with female sex, non-smoking history, autoantibody positivity, and CTD symptoms (p = 0.01, 0.03, 0.01, and 0.04, respectively). CONCLUSIONS: patients with IPF with pathological findings of CTD showed clinical characteristics similar to those of patients with CTD.

DOI： 10.3390/diagnostics11081359

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a fibrotic disease of unknown aetiology with a poor prognosis. Several clinical trials of nintedanib in patients with IPF have reported its inhibitory effect on reduced lung function, incidence of acute exacerbation of IPF and worsened health-related quality of life. Although nintedanib has a manageable safety and tolerability profile over long-term use, it was discontinued in over 20% of patients because of adverse events such as diarrhoea and liver dysfunction. This might explain why nintedanib use in patients with IPF is not widespread, especially among patients with early-stage IPF. In the present study, we aimed to clarify the efficacy, safety and tolerability of nintedanib in patients with stage I/II IPF, based on the Japanese IPF disease severity staging classification system. METHODS AND ANALYSIS: This is an ongoing, prospective, multicentre observational cohort study of patients with stage I/II IPF who will start receiving nintedanib. Totally, 215 patients at 35 sites in Kyushu and Okinawa, Japan will be enrolled and followed up for 3 years. Nintedanib therapy would be initiated at the discretion of the investigator. The primary endpoint, change in forced vital capacity (FVC) at 156 weeks, will be shown as the mean change in FVC from baseline to week 156 with 95% CIs estimated using the Wald method. The safety endpoint-occurrence of adverse events-will be assessed in each system organ class/preferred term. ETHICS AND DISSEMINATION: The study protocol and informed consent documents were approved by the Institutional Review Board at Nagasaki University Hospital (approval number 19102146) and each participating site. Written informed consent was obtained from all participants. Patient recruitment has begun. The results will be disseminated through scientific peer-reviewed publications and national and international conferences. TRIAL REGISTRATION NUMBER: UMIN000038192.

DOI： 10.1136/bmjopen-2020-047249

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Authorship：Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/cmdc.202100064

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cmdc.202100064

Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/joim.13154

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Influenza pneumonia, which causes acute respiratory distress syndrome and multiple organ failure, has no established management protocol. Recently, corticosteroid therapy was used to treat coronavirus disease 2019 with respiratory failure; however, its effectiveness as a treatment for influenza pneumonia remains controversial. To investigate the impact of corticosteroid therapy for the early phase of severe influenza pneumonia, we compared influenza pneumonia patients with respiratory failure treated with or without corticosteroids within 7 days after hospital admission using a Japanese nationwide administrative database. The primary endpoint was the mortality rate. The secondary endpoints were duration of intensive-care unit management, invasive mechanical ventilation, and hospital stay. The inverse probability weighting method with estimated propensity scores was used to minimize the data collection bias. We included 3519 patients with influenza pneumonia with respiratory failure. Of these, 875 were treated with corticosteroids. There was no significant difference between the groups regarding 30-day and 90-day mortality, duration of intensive-care unit management, invasive mechanical ventilation, and hospital stay. However, the in-hospital mortality rate was higher in the corticosteroid group. The use of systematic corticosteroid therapy in patients with influenza pneumonia was associated with a higher in-hospital mortality rate.

DOI： 10.3390/jcm10030494

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Language：Japanese   Publisher：Microbiology Spectrum  

Invasive aspergillosis in immunocompromised individuals is associated with a poor prognosis. Recently, the global emergence of azole-resistant Aspergillus fumigatus has underscored the urgent need for novel therapeutic strategies beyond conventional small-molecule antifungal agents. Natural killer (NK) cells, which are characterized by the absence of CD3 and presence of CD56 surface markers, play a pivotal role in the immune response against fungal pathogens and in the elimination of malignant cells and virus-infected host cells. Although the antifungal activity of NK cells against Aspergillus spp. and other fungi has been demonstrated, the efficacy of ex vivo-expanded human NK cells against azole-resistant A. fumigatus has not been investigated. NK cells, which were expanded from the CD3- peripheral blood mononuclear cells obtained from healthy donors, were co-cultured with fungi. Antifungal activity was assessed using the 2,3-(bis2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxyanilide reduction assay. NK cells demonstrated antifungal activity against azole-resistant A. fumigatus and other filamentous fungi. These findings suggest that a direct interaction between NK cells and hyphae is critical for exerting antifungal effects, with degranulation likely contributing to the underlying mechanism. However, contrary to previous reports, we failed to observe the direct antifungal activity of interferon-γ secreted by NK cells under our experimental conditions. Cellular immunotherapy using NK cells may represent a promising therapeutic approach for the treatment of azole-resistant aspergillosis.IMPORTANCEAspergillus fumigatus is a ubiquitous fungus that causes invasive aspergillosis (IA) in immunocompromised patients, with poor prognosis. Furthermore, azole-resistant A. fumigatus has spread globally in recent years. The present antifungal drugs pose challenges such as drug resistance and adverse events; thus, the development of novel therapies for IA is needed beyond the antifungal drugs. In cases of IA in immunocompromised patients with poor response to antifungal drugs, cellular immunotherapy is a reasonable approach. This study demonstrated that human natural killer (NK) cells derived from peripheral blood exhibit antifungal activity against azole-resistant A. fumigatus comparable to that of azole-susceptible strain. This indicates that cellular immunotherapy using NK cells could become an effective therapy for IA caused by azole-resistant A. fumigatus. Investigating the mechanism by which NK cells exhibit antifungal activity against A. fumigatus could lead to the development of novel therapies for IA.

DOI： 10.1128/spectrum.03372-25

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Language：Japanese   Publisher：American Journal of Medicine  

DOI： 10.1016/j.amjmed.2025.11.003

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.resinv.2026.101423

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Language：Japanese   Publisher：Journal of Thoracic Disease  

Background: Environmental fungi, particularly basidiomycetes, have been proposed to contribute to fungus-associated chronic cough (FACC), but the association remains incompletely substantiated and may vary by region and season. Therefore, we performed fungal cultures of spontaneous sputum from patients with unexplained or refractory chronic cough (UCC/RCC) in the Nagasaki region and investigated associations between basidiomycete detection and monthly temperature and humidity. Methods: Thirty patients with UCC/RCC and 30 patients with other respiratory diseases without chronic cough (CC) underwent spontaneous sputum collection and fungal culture. Participants completed a cough/ sputum symptom questionnaire [cough visual analog scale (VAS) and chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) questions 1–2], underwent chest computed tomography, and were assessed for comorbidities and medications. We compared (I) CC vs. non-chronic cough (NC) groups and (II) basidiomycete-positive vs. basidiomycete-negative patients within the CC group. Results: Basidiomycetes were detected in sputum samples from 9 of 30 patients (30.0%) in the CC group, whereas none were detected in the NC group (P=0.002). Basidiomycetes were primarily detected in samples collected between June and August and the monthly detection rate showed a significant correlation with monthly humidity and temperature. Within the CC group, no significant differences were observed between basidiomycete-positive and -negative patients regarding demographics, smoking history, underlying diseases, medication use, symptom scores, or high-resolution computed tomography (HRCT) findings. Conclusions: In the Nagasaki region, basidiomycete-positive sputum cultures were significantly more frequent in patients with CC than in patients without CC. A basidiomycete species profile different from previously reported profiles was observed, and detection frequency showed seasonal correlation with temperature and humidity in this cohort. These findings suggest the importance of proactively performing fungal cultures while considering regional and seasonal factors when evaluating possible FACC.

DOI： 10.21037/jtd-2025-1-2716

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/rap/rkag021

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.resinv.2026.101392

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Language：English   Publisher：エルゼビア・ジャパン(株)  

Language：Japanese   Publisher：Journal of Thoracic Disease  

Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by airflow limitation and exertional dyspnea, leading to reduced exercise tolerance and physical inactivity. Nasal high-flow (NHF) therapy delivers heated and humidified gas at a high flow rate through a nasal cannula, washing out anatomical dead space, providing a small degree of positive airway pressure, improving ventilation efficiency, and reducing the work of breathing. In addition, adequate humidification may enhance ciliary clearance. The AIRVO3^TM (Fisher & Paykel Healthcare, Auckland, New Zealand) is a novel portable NHF device that incorporates these features and can be used during ambulation. Using AIRVO3^TM during exertion may improve exercise tolerance in patients with COPD; however, its safety and effectiveness in ambulatory patients have not yet been established. Methods: This is a single-center, early-phase, open-label, randomized, two-period crossover pilot trial conducted at Nagasaki University Hospital, designed to evaluate the acute, within-day effects of AIRVO3^TM on exercise tolerance during a single visit. Twenty patients with moderate to severe COPD will perform two 6-minute walk tests (6MWT) in a randomized order: one with AIRVO3^TM and one without the device. The primary outcome is the 6-minute walk distance (6MWD). Secondary outcomes include percutaneous oxygen saturation (SpO<inf>2</inf>), transcutaneous partial pressure of carbon dioxide (PtcCO<inf>2</inf>), respiratory rate, pulse rate, Borg dyspnea scale score, time to desaturation (SpO<inf>2</inf> ≤90%), time to PtcCO<inf>2</inf> ≥45 mmHg, time to respiratory rate ≥22/min, walking distance to the first rest, patient-reported comfort, and subjective symptoms. Safety outcomes include the incidence of SpO<inf>2</inf> <90%, adverse events (AEs), device-related discomfort, and withdrawal or dropout. Data will be analyzed primarily using paired t-tests and mixed-effects models that are appropriate for a crossover design. Discussion: This trial will evaluate whether a portable NHF device increases exercise tolerance and is safe during ambulation in patients with COPD who do not require long-term oxygen therapy. By using room air [fraction of inspired oxygen (FiO<inf>2</inf>) 21%] and focusing on high flow rather than high oxygen concentration, this study will clarify the pure effects of high-flow nasal therapy on exertional capacity. If the AIRVO3^TM device is shown to be effective and acceptable, it may expand the options for pulmonary rehabilitation and daily physical activity in patients with COPD. Because all assessments are performed during a single study visit, this trial specifically evaluates short-term, acute responses to AIRVO3^TM rather than long-term training effects of repeated use.

DOI： 10.21037/jtd-2025-aw-2316

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Background

Ventilator-associated pneumonia (VAP) is a fatal intensive care infection. VAP caused by methicillin-resistant Staphylococcus aureus (MRSA) can be exacerbated by Prevotella intermedia culture supernatant ( P. int. sup.). Solithromycin (SOL), a fourth-generation macrolide, inhibits bacterial protein synthesis and modulates immunity; however, its effects on exacerbation of MRSA-VAP by P. int . sup. remain unclear. This study examined whether SOL inhibits bacterial protein synthesis by binding to the 50S ribosomal subunits in P. int . sup. and subsequently reduces the worsening of MRSA-VAP caused by P. int. sup.

Methods

BALB/cCrSlc mice received MRSA and P. int. sup. with or without sub-minimum inhibitory concentrations of SOL ( P. int . sup. (SOL)) or clarithromycin (CAM; P. int. sup. (CAM)). Outcomes included survival rates, lung MRSA burden, and transcriptomics (reverse transcription polymerase chain reaction, bulk RNA sequencing [RNA-seq]). In vitro , bone marrow-derived alveolar macrophage-like cells (AMLCs) from C57BL/6J mice were infected with MRSA ± SOL; bactericidal activity and mRNA expression were measured.

Results

P. int . sup. increased mortality, bacterial load, and neutrophilic infiltration; however, P. int . sup. (SOL) significantly improved survival rate (100%, n = 8, ****P &amp;lt; 0.0001), reduced MRSA burden ( n = 10–11, **P &amp;lt; 0.01), and enhanced macrophage recruitment ( n = 7–8, ****P &amp;lt; 0.001). P. int. sup. downregulated Ccr2 expression ( n = 7–8, ***P &amp;lt; 0.001). RNA-seq analysis revealed P. int . sup. (SOL) upregulated macrophage phagocytosis and bactericidal pathways. SOL-pretreated AMLCs infected with MRSA exhibited reduced bacterial burden ( n = 8, *P &amp;lt; 0.05 vs control, **P &amp;lt; 0.01 vs CAM-pretreated AMLCs) and upregulated Tnf-α expression ( n = 7–8, *P &amp;lt; 0.05 vs control).

Conclusion

SOL protects by activating alveolar macrophages and promoting TNF-related responses, suggesting a novel immunomodulatory role for SOL in host defense against exacerbation of MRSA-VAP by P. int. sup.

DOI： 10.3389/fcimb.2026.1723186

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ejca.2026.116232

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Abstract

Background

Bacteroides species are significant anaerobes that cause intra-abdominal infections. Recent data highlight increasing resistance, specifically to clindamycin (CLDM). However, the precise epidemiology of Bacteroides fragilis and non-fragilis remains unclear.

Methods

We retrospectively analyzed 528 obligate anaerobes that were isolated from blood cultures at 6 major Japanese hospitals between 2012 and 2022, with 102 B. fragilis and 72 non-B. fragilis isolates. Clinical characteristics and antimicrobial resistance were assessed. Drug resistance rates over time were analyzed using the Spearman rank correlation test.

Results

Compared with the B. fragilis group, non-B. fragilis group demonstrated higher resistance to CLDM (P = .006) and carbapenem (P = .005). Excluding deaths from underlying diseases, the 30-day mortality rate was higher in the non-B. fragilis group than in the B. fragilis group (P = .025). Risk factors in this group included carbapenem resistance (adjusted odds ratio = 7.05, P = .017). Notably, carbapenem (P = .014 vs P = .643) and tazobactam/piperacillin resistance rates (P = .012 vs P = .899) increased over time in the non-B. fragilis group, rather than the B. fragilis group.

Conclusions

Non-B. fragilis shows increasing resistance to key antibiotics and is linked to higher 30-day mortality compared with B. fragilis.

DOI： 10.1093/ofid/ofag047

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Other Link： https://academic.oup.com/ofid/article-pdf/13/2/ofag047/66647365/ofag047.pdf

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Synovial sarcoma (SS) is a rare soft tissue sarcoma (STS) with limited treatment options, indicating the need for novel therapeutic strategies. In this study, we investigated the efficacy of talazoparib, a poly (ADP-ribose) polymerase enzyme (PARP) inhibitor, and DNA damage response (DDR) inhibitors in SS in vitro. METHODS: To investigate the target gene of talazoparib, we examined the mRNA expression of PARP1 and PARP16 in SS, using data from the Gene Expression Omnibus (GEO) database. Cell viability was assessed to evaluate the efficacy and antitumor effects of talazoparib and other drugs in multiple SS cell lines, using MTT assay. Additionally, flow cytometry-based annexin V assay and western blotting were performed to assess cell apoptosis and protein expression levels, respectively. RESULTS: mRNA expression of PARP16 was slightly higher in SS than other STS from GEO profile database. Talazoparib exerts anticancer effects against SS cells with high PARP16 expression by inducing apoptosis and DNA damage, on the other hand, the effects of talazoparib may be limited in SS cells with low PARP16 expression. Treatment with other DDR inhibitors, such as CHK1, WEE1, and ATR, suppressed the proliferation of SS cells. Celarasertib inhibited ATR phosphorylation and induced the cleavage of PARP and γH2AX, suggesting that celarasertib induced DNA damage and cell apoptosis. Combined therapy with talazoparib and ceralasertib exerts antitumor effects against SS cells through DNA damage and apoptosis pathways, suggesting a potential treatment strategy for SS. CONCLUSION: Talazoparib combined with ATR inhibitor possesses potential application as a therapeutic option for SS.

DOI： 10.1007/s12672-026-04422-5

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BACKGROUND: Chronic obstructive pulmonary disease (COPD), a major global health burden linked to smoking, is frequently underdiagnosed due to low awareness and delayed symptom recognition. This study explored the feasibility of non-invasive voice and cough sound analysis for COPD identification. METHODS: In this prospective study, 55 participants (26 with COPD, 29 without) underwent pulmonary function testing and provided sociodemographic and clinical data. Speech and cough sounds were recorded three times per participant and processed using acoustic feature extraction, feature selection via the minimum redundancy maximum relevance algorithm, and logistic regression classification. Model performance was evaluated using four-fold cross-validation. Statistical analysis was conducted with JMP software (p < 0.05). RESULTS: The vowel sound/u/showed statistically significant discriminatory ability in the mixed-gender cohort, but sensitivity and specificity were both below 80 %, indicating limited diagnostic performance. When restricted to male participants, both metrics exceeded 80 %, suggesting higher discriminatory power. Smartphone recordings yielded comparable accuracy to integrated circuit recorders. Adding COPD assessment test scores and smoking history did not improve classification. CONCLUSIONS: Voice analysis may offer a non-invasive screening approach for COPD. However, this study was limited to male participants and a single disease target, restricting generalizability. Future research will expand to include related respiratory conditions such as bronchiectasis and assess performance across sexes and disease types.

DOI： 10.1016/j.resinv.2025.101353

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Language：Japanese   Publisher：Therapeutic Advances in Infectious Disease  

Background: Coronavirus disease 2019 (COVID-19) remains an epidemic worldwide, and long COVID is a major social concern. Therapeutic options for relieving symptoms of COVID-19 pneumonia are limited. Clarithromycin (CAM), a macrolide antimicrobial, also functions as an immunomodulator. Objectives: To assess the efficacy of CAM in improving clinical symptoms and attenuating inflammation in patients with mild COVID-19, with the aim of preventing progression to severe disease. Design: An exploratory, multicenter, randomized-controlled, open-label trial. Methods: This trial enrolled patients with mild COVID-19 pneumonia without oxygen supplementation from May 2021 through February 2022 in eight hospitals in Japan. Patients were randomly assigned in a 1:1:1 ratio to groups A (CAM 800 mg/day, 7 days), B (CAM 400 mg/day, 7 days), or C (standard treatment). The primary endpoint was the number of days required for 50% improvement in seven symptoms (fatigue, headache, cough, shortness of breath, taste/smell disturbance, and general unwellness) based on severity scores. Secondary endpoints included inflammatory cytokines, viral load, immunoglobulins, and pneumonia infiltrations. Results: A total of 56 patients were enrolled and randomized. The primary endpoint did not differ significantly between groups (A: 5.0 days, B: 4.0 days, C: 4.0 days), though the seven symptoms tended to disappear earlier in group A than group C (p = 0.08), and fatigue significantly decreased in group A (p = 0.005). Serum inflammatory cytokines, tumor necrosis factor (TNF)-α, granulocyte colony stimulating factor (G-CSF), interleukin (IL)-7, IL-15, and proliferation factors, transforming growth factor (TGF)-α, fibroblast growth factor (FGF)-2, and fms-like tyrosine kinase 3 ligand (Flt3-L), significantly decreased in group A. IL-8 and IFN-γ in nasal drip significantly decreased in both group A and B. Serious adverse events did not increase in CAM groups, though mild gastrointestinal and liver events occurred in group A. Conclusion: CAM is safe and potentially useful for improving partial COVID-related symptoms and exerting immunomodulation during COVID-19 pneumonia. Trial registration: Japan Registry of Clinical Trials (jRCT; registration number: jRCTs071210011; https://jrct.mhlw.go.jp/latest-detail/jRCTs071210011) on April 13, 2021.

DOI： 10.1177/20499361261431488

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Language：English   Publisher：エルゼビア・ジャパン(株)  

Language：Japanese   Publisher：Renal Failure  

In 2018, the Antineutrophil Cytoplasmic Antibody (ANCA) Renal Risk Score (ARRS) was proposed as a prognostic tool for renal outcomes in patients with ANCA-associated glomerulonephritis (AAGN). Subsequently, a revised version of the ANCA Kidney Risk Score (AKRiS) was reported in 2024. Nonetheless, its usefulness in Japanese patients has not yet been evaluated. We retrospectively analyzed 109 patients with biopsy-proven AAGN (mean age, 69 years; 50% male) from 13 institutions in Nagasaki Prefecture between January 1995 and December 2019. The prognostic performance of both the ARRS and AKRiS for end-stage kidney disease was assessed using Kaplan–Meier analysis, log-rank test, and receiver operating characteristic (ROC) curve analysis. Myeloperoxidase-ANCA positivity was observed in 90.8% of patients. Based on the AKRiS, 47, 39, 15, and 8 patients were classified as low-, medium-, high-, and very high-risk, respectively. The median observation period was 863 days (interquartile range 254.5–2034). Both the ARRS and AKRiS groups demonstrated progressively worse renal survival with increasing risk categories (both p < 0.001). In the ROC analysis, the area under the curve was 0.76 and 0.82 for ARRS and AKRiS, respectively. AKRiS may be a useful prognostic tool for renal outcomes in Japanese patients with AAGN, potentially providing better predictive accuracy compared to the ARRS.

DOI： 10.1080/0886022X.2026.2678630

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Language：Japanese   Publisher：Frontiers in Cellular and Infection Microbiology  

Introduction: The global prevalence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing. Individuals with NTM-PD frequently develop chronic pulmonary aspergillosis, which is associated with poor clinical outcomes. However, the biological mechanisms underlying the interaction between Aspergillus species and non-tuberculous mycobacteria (NTM) remain poorly understood. This study aimed to investigate the interaction between Aspergillus fumigatus and NTM and to identify mechanisms that may inform novel therapeutic strategies. Methods: A. fumigatus was incubated with NTM culture supernatants, and biofilm formation was quantified using the crystal violet assay. Phagocytic activity against A. fumigatus conidia were assessed in THP-1-derived macrophages infected with Mycobacterium avium. Conversely, phagocytosis of M. avium was evaluated in macrophages exposed to A. fumigatus culture supernatants. Finally, fungal clearance in vivo was assessed in mice pre-infected with M. avium. Results: NTM supernatants significantly enhanced A. fumigatus growth. M. avium infection decreased the macrophages-phagocytosis rate of A. fumigatus by approximately 40% compared to uninfected control. Additionally, M. avium infection reduced Dectin-1 gene expression in macrophages by half. Secondary metabolites produced by A. fumigatus impaired macrophage phagocytosis of M. avium. In vivo, prior M. avium infection delayed fungal clearance from the lungs. Discussion: NTM promote not only A. fumigatus growth but also its colonization by impairing macrophage immune function. Conversely, A. fumigatus suppresses host defense against NTM via secondary metabolites. These findings suggest that microbial cross-modulation creates a permissive niche that facilitates co-colonization and may contribute to disease progression.

DOI： 10.3389/fcimb.2026.1810773

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Language：Japanese   Publisher：Frontiers in Immunology  

Background – Acute exacerbation of rheumatoid arthritis–associated interstitial lung disease (AE-RA-ILD) is a life-threatening condition for which no standard therapy has been established. Although Janus kinase (JAK) inhibitors are effective for treating rheumatoid arthritis (RA) and have shown potential benefit in chronic RA-ILD, evidence supporting their use in AE-RA-ILD remains extremely limited. Methods – This retrospective observational study included consecutive patients hospitalized for AE-RA-ILD who received JAK inhibitors alongside systemic glucocorticoids between January and December 2024. Clinical characteristics, laboratory data, treatment regimens, and outcomes were extracted from medical records. High-resolution computed tomography images were quantitatively evaluated at three time points—before acute exacerbation (AE), at exacerbation onset, and after treatment—using a standardized computed tomography (CT) scoring system. Results – Six patients with AE-RA-ILD were included. In five of the six cases, the JAK inhibitor was discontinued due to an adverse event prior to AE onset, with a median interval of 9 days between discontinuation and AE onset. Upadacitinib was administered to four patients, and baricitinib to two patients. Three patients received methylprednisolone pulse therapy. Respiratory status improved in all patients, as indicated by increases in the PaO<inf>2</inf>/FiO<inf>2</inf> ratio. The total CT score increased from baseline (175.3 ± 50.3) to AE onset (247.2 ± 53.6) and subsequently decreased after treatment (220.1 ± 58.6), with notable improvement in fibrotic lesion components. All patients survived during the 3-month observation period, although four patients experienced a decline in percent predicted forced vital capacity, and three required home oxygen therapy at discharge. Conclusion – In this retrospective case series, adjunctive treatment with JAK inhibitors was associated with improvements in respiratory status and radiological findings in patients with AE-RA-ILD. These findings suggest that JAK inhibitors may represent a promising therapeutic option for this severe condition and support the need for further investigation in larger, prospective studies.

DOI： 10.3389/fimmu.2026.1800161

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) frequently develop rapidly progressive interstitial lung disease and may also exhibit hepatic dysfunction, yet the mechanisms of hepatic injury remain poorly defined. We investigated the roles of M2-like macrophages and complement activation in hepatic injury associated with anti-MDA5 antibody-positive DM. METHODS: Liver specimens from five autopsy cases of anti-MDA5 antibody-positive DM were examined for the presence of CD80-positive M1-like and CD206-positive M2-like macrophages. To establish a model of antibody-mediated hepatic injury, human MDA5 transgenic mice were treated with in-house anti-human MDA5 monoclonal antibodies. The contribution of complement was assessed by comparing hepatic pathology between wild-type and complement component C3-deficient MDA5 transgenic mice. Liver tissues were analyzed by immunohistochemistry and western blotting, and single-cell RNA sequencing libraries were generated from snap-frozen mouse liver samples. RESULTS: Autopsy liver specimens demonstrated the presence of CD80-positive M1-like and CD206-positive M2-like macrophages. In human MDA5 transgenic mice, administration of anti-human MDA5 monoclonal antibodies induced hepatic injury accompanied by increased infiltration of CD206-positive M2-like macrophages. This hepatic injury was markedly attenuated in C3-deficient MDA5 transgenic mice, supporting an important role for complement activation in this model. CONCLUSION: Complement activation and the accumulation of M2-like macrophages are associated with anti-human MDA5 monoclonal antibody-induced hepatic injury in mice. These findings provide mechanistic insight into antibody-complement-macrophage interactions and suggest that modulation of complement pathways may represent a potential therapeutic approach to limit liver and systemic involvement in this disorder.

DOI： 10.3389/fimmu.2026.1707202

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Language：Japanese   Publisher：Frontiers in Immunology  

Background: Activation of the α7 nicotinic acetylcholine receptor (α7nAChR) exerts anti-inflammatory effects; however, its role in allergic airway inflammation remains poorly understood. This study investigated how GTS-21 treatment, consistent with α7nAChR activation, influences airway inflammation and epithelial cytokine responses. Methods: A murine model of allergic airway inflammation was established in female C57BL/6J mice by repeated house dust mite (HDM) exposure. Mice received intratracheal GTS-21 or phosphate-buffered saline (PBS) prior to each HDM challenge. Airway inflammation and cytokine levels were then evaluated. In vitro, BEAS-2B human airway epithelial cells were treated with GTS-21 or PBS, followed by stimulation with HDM and lipopolysaccharide (LPS). Thymic stromal lymphopoietin (TSLP) production was quantified, and RNA sequencing was performed to analyze gene expression changes. Results: Intratracheal GTS-21 administration significantly attenuated HDM-induced eosinophilic airway inflammation in mice and reduced TSLP and type 2 cytokine levels. In BEAS-2B cells, GTS-21 treatment similarly suppressed LPS- and HDM-induced TSLP production. RNA sequencing revealed that GTS-21 treatment upregulated heme oxygenase-1 (HO-1) expression. Increased HO-1 expression was associated with reduced TSLP production under these experimental conditions. Conclusion: GTS-21 attenuated allergic airway inflammation and suppressed epithelial TSLP production in association with increased HO-1 expression. These findings suggest that cholinergic receptor-associated signaling may modulate epithelial inflammatory responses in allergic airway inflammation.

DOI： 10.3389/fimmu.2026.1808271

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1080/0886022X.2025.2578417

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Language：Japanese   Publisher：Internal Medicine Tokyo Japan  

DOI： 10.2169/internalmedicine.5216-24

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Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is still an ongoing public health threat. COVID-19 can be accompanied by prolonged symptoms, known as "long COVID", however, no pharmaceutical treatments are currently available for these symptoms. Lactococcus lactis strain Plasma (LC-Plasma; Lactococcus lactis subsp. lactis JCM 5805) directly activates human plasmacytoid dendritic cells (pDCs) and triggers antiviral immune responses. We hypothesized that LC-Plasma reduced SARS-CoV-2 viral load and eased symptoms in patients with mild COVID-19. METHODS: This PLATEAU study enrolled 100 patients with mild COVID-19 during Omicron BA.1 endemic, who were randomized into the LC-Plasma or placebo group in a 1:1 ratio and were observed for 14 days. The primary endpoint was change in total score of eight subjective symptoms (fatigue, anorexia, headache, cough, shortness of breath, chest pain, smell, and taste disturbance). Secondary endpoints included each symptom, SARS-CoV-2 viral load, and pDCs. RESULTS: The primary endpoint did not show between-group differences. However, the proportion of patients without smell and taste disturbances was significantly higher in the LC-Plasma group on day 13 (p = 0.030). The LC-Plasma group showed a significantly earlier decrease in SARS-CoV-2 viral load on day 4 (p < 0.001) and an increase in pDCs on day 8 (p = 0.0498). Mild adverse events, such as diarrhea, cough-variant asthma, and urticaria, occurred in three (5.9%) patients in the LC-Plasma group. CONCLUSIONS: The intake of LC-Plasma in patients with mild COVID-19 activates pDC, decreases SARS-CoV-2 viral load earlier, and may improve smell and taste disorders more quickly. LC-Plasma could be a safe, inexpensive, and easily accessible tool for the treatment of mild COVID-19. TRIAL REGISTRATION: jRCTs071210097.

DOI： 10.1007/s40121-025-01246-8

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.clinthera.2025.10.005

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BACKGROUND: Whole slide imaging (WSI) is digital imaging technique that involves scanning glass slides. Although WSI is widely used in pathological diagnosis and education, its impact on nephrology education remains unknown. We clarified the usefulness of WSI in rapid treatment decision-making and education in renal pathology. METHODS: We included in patients undergoing renal biopsy at our facility and divided them into two groups: the WSI (-) group, underwent renal biopsy during (July, 2020-June, 2022), when WSI was not available, and the WSI (+) group (July, 2022-June, 2024), when WSI was available on electric medical record. The time from renal biopsy to the description of the pathological assessment, days to treatment initiation or modification, and the percentage of the assessment reported by nephrology trainees were compared between the two groups. Furthermore, this study included an inquiry about the usefulness of WSI from nephrologists who worked during these periods. RESULTS: The time until assessment description and treatment initiation or modification were shorter in the WSI (+) group (p < 0.001 for both). Multivariable Cox regression analysis showed that the use of WSI had the most significant impact on these outcomes (p < 0.001). Moreover, the percentage of first assessments reported by nephrology trainees increased from 25.8% to 53.2% (p < 0.001), and multivariable logistic analysis showed that WSI was the most associated factor (p < 0.001). In the questionnaire, most nephrologists cited the ease of access and sharing as the main advantages of WSI. CONCLUSIONS: WSI is helpful for rapid treatment decision-making and education in renal pathology.

DOI： 10.1007/s10157-025-02710-y

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Diagnosing pulmonary lymphoma is challenging and often requires surgical procedures. Molecular analysis of bronchoalveolar lavage fluid (BALF) may facilitate pulmonary lymphoma diagnosis; however, many aspects of this technique remain unknown. We aimed to establish a molecular diagnosis strategy for pulmonary lymphomas using BALF. METHODS: The following molecular analyses were performed using BALF from 62 patients (eight with adult T-cell leukaemia/lymphoma (ATLL) and 11 with B-cell lymphoma): flow cytometric analysis; T-cell and B-cell clonality based on immunoglobulin heavy chain (IGH) and T-cell receptor (TCR) rearrangements; and fluorescence in situ hybridisation (FISH) analysis of IGH, mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1), B-cell lymphoma 2 (BCL2), and myelocytomatosis (MYC) oncogene. RESULTS: CD25 and tumour suppressor in lung cancer-1 marker levels were significantly elevated in ATLL cases at a median of 37.8% and 33.0%, respectively, with 100% positive TCR rearrangements. Notably, FISH analysis showed numerical chromosomal abnormalities in at least one of the genes in 87.5% of patients. In B-cell lymphoma, CD19 and CD20 marker levels were significantly elevated at 4.2% and 14.3%, respectively. The sensitivity and specificity of IGH rearrangements were 81.8% and 85.4%, respectively. FISH analysis detected translocations in at least one of the genes in 45.5% of patients. CONCLUSIONS: Numerical chromosomal abnormalities in the BALF of patients with ATLL and gene translocations in B-cell lymphoma are specific and novel findings. Molecular analysis of BALF is expected to be incorporated into a diagnostic system for pulmonary lymphoma to achieve low invasiveness and improve diagnostic accuracy.

DOI： 10.1183/23120541.01377-2024

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Language：English   Publisher：エルゼビア・ジャパン(株)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.resinv.2025.10.010

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Language：English   Publisher：エルゼビア・ジャパン(株)  

Language：Japanese   Publisher：Respiratory Investigation  

Humidifier lung is a type of hypersensitivity pneumonitis caused by repeated inhalation of contaminated humidifier vapor containing antigens. Identification of specific antigens is crucial for the management of hypersensitivity pneumonitis. We report a case of humidifier lung in a 60-year-old man who presented with fever and dyspnea. Bacteriological examination of the humidifier identified Cryptococcus laurentii and antigen identification using the precipitating antibody method was positive for C. laurentii. Although C. laurentii is known to cause opportunistic infections, this case suggests that it may also be a potential causative antigen of humidifier lung in non-immunosuppressed individuals.

DOI： 10.1016/j.resinv.2025.08.003

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.resinv.2025.08.003

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Language：English   Publisher：(一社)日本腎臓学会  

腎病理における治療方針決定の迅速化と修練医教育にwhole slide imaging(WSI)が有用か検討した。当院で腎生検を行った307例を、WSI施行群156例と非施行群151例に分類した。腎生検から病理評価までの日数は、WSI施行群が15.1±14.7日で、WSI非施行群28.1±21.2日と比較して有意に短かった。多重Cox回帰分析では、WSIは評価までの期間短縮と有意に関連していた。また、病理所見をもとに治療を開始した250例の解析では、腎生検から治療開始までの日数はWSI施行群が29.3±25.7日で、WSI非施行群50.4±39.9日と比較して有意に短縮していた。修練医による評価報告率も、WSIの導入によって25.8%から53.2%へ顕著に増加し、有意差を認めた。WSIは非常に有用な手法であると考えられた。

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1186/s12931-025-03379-3

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Other Link： https://link.springer.com/article/10.1186/s12931-025-03379-3/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Early diagnosis of invasive aspergillosis (IA) is critical for the initiation of effective antifungal therapy. Currently, detection of galactomannan (GM), a secreted fungal glycan, is the most used culture-independent diagnostic test for IA. However, limitations in the sensitivity and specificity of this test have led to interest in identifying other target molecules. Galactosaminogalactan (GAG), a polysaccharide cell wall component secreted by Aspergillus hyphae, is a potential diagnostic marker for IA. OBJECTIVES: To evaluate the utility of GAG as a diagnostic target, we generated a monoclonal antibody against GAG (mAb 1D1), established a GAG enzyme-linked immunosorbent assay (ELISA), evaluated its cross-reactivity with other respiratory pathogens, and compared the performance of the GAG detection ELISA with GM antigen detection in both an in vivo mouse model and human samples from patients with pulmonary aspergillosis. RESULTS: The GAG ELISA demonstrated strong reactivity with culture supernatants from Aspergillus fumigatus and Aspergillus flavus but limited reactivity with culture supernatants of other Aspergillus spp. and non-Aspergillus filamentous fungi. In a mouse model of IA, GAG was detected in lung tissue, serum, bronchoalveolar lavage fluid (BALF), and urine samples. Although GAG was detected by mAb 1D1 staining of Aspergillus hyphae in infected human lung tissue samples, it was not detectable in the serum, BALF, and urine of patients with pulmonary aspergillosis. CONCLUSIONS: Further studies are required to determine whether the failure to detect GAG in the serum, BALF, and urine of patients with pulmonary aspergillosis is due to absence or low GAG levels or other reasons.

DOI： 10.1111/myc.70125

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：European Respiratory Society (ERS)  

Objective Progressive pulmonary fibrosis (PPF) is a chronic interstitial lung disease (ILD) characterized by fibrotic progression and poor prognosis, with effective treatment strategies for previously untreated patients remaining unclear. This study evaluated the efficacy and safety of upfront combination therapy with anti-inflammatory and antifibrotic agents in previously untreated PPF patients.

Methods This multicenter, single-arm phase 2 study enrolled 34 patients with ILD—including unclassifiable idiopathic interstitial pneumonia, idiopathic nonspecific interstitial pneumonia, fibrotic hypersensitivity pneumonitis, and rheumatoid arthritis–associated ILD—all with evidence of PPF. Tacrolimus (0.0375 mg·kg⁻¹ twice daily) and prednisolone (10 mg once daily) were initiated on day 1, with nintedanib (150 mg twice daily) added on day 8. The tacrolimus dosage was adjusted to maintain blood trough levels. The primary endpoint was the change in the relative decline slope for forced vital capacity % predicted (%FVC) between before and after treatment.

Results The protocol treatment was associated with a substantial improvement in the relative %FVC decline slope, from −20.9%/year before to +11.2%/year after treatment. Subgroup analysis revealed greater improvement in patients with an increased lymphocyte percentage in bronchoalveolar lavage fluid or elevated blood biomarkers. Adverse events, such as diarrhea (67.6%) and hepatic dysfunction (29.4%), were manageable, with no severe cases or treatment discontinuations.

Conclusion Early combination therapy with tacrolimus, prednisolone, and nintedanib was associated with improved pulmonary function and was well tolerated in previously untreated PPF patients. Our findings suggest the potential of this regimen as an initial treatment strategy, but further validation in larger randomized controlled trials is warranted.

DOI： 10.1183/23120541.00697-2025

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Language：English  

DOI： 10.1007/s00535-025-02275-3

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Language：English   Publishing type：Research paper (scientific journal)  

Humidifier lung is a type of hypersensitivity pneumonitis caused by repeated inhalation of contaminated humidifier vapor containing antigens. Identification of specific antigens is crucial for the management of hypersensitivity pneumonitis. We report a case of humidifier lung in a 60-year-old man who presented with fever and dyspnea. Bacteriological examination of the humidifier identified Cryptococcus laurentii and antigen identification using the precipitating antibody method was positive for C. laurentii. Although C. laurentii is known to cause opportunistic infections, this case suggests that it may also be a potential causative antigen of humidifier lung in non-immunosuppressed individuals.

DOI： 10.1016/j.resinv.2025.08.003

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The precise mechanisms of respiratory infection caused by oral anaerobic bacteria remain elusive. Unexpectedly, bacterial microbiota analysis with 16S rRNA revealed "hidden" mixed infections of anaerobic bacteria and commensal oral Streptococcus species in patients with community-acquired pneumonia. The study aimed to elucidate the mechanisms by which Prevotella intermedia exacerbates oral streptococcal pneumonia. METHODS: Oral streptococci were oropharyngeally administered with the culture supernatants of P intermedia (PiSup) in mice to assess survival, microbial burden, inflammatory responses, and host response via unbiased bulk RNA sequencing. Additionally, genetically engineered strains of P intermedia were used to identify pathogenic factors. RESULTS: Seven-week-old female C57BL/6J mice treated with the combination of Streptococcus spp and PiSup exhibited significantly worse survival and increased microbial burden in the lungs and spleen when compared with Streptococcus spp and control medium. RNA sequencing of whole lung revealed disruption of neutrophilic bactericidal activity due to NADPH downregulation, accompanied by reduced myeloperoxidase production in mixed infections, leading to dysfunctional neutrophil accumulation in the lungs. Notably, PiSup from strains bearing mutations in the type IX secretion pathway (ΔporT or ΔporK) failed to worsen the mixed infection. CONCLUSIONS: P intermedia exacerbates pneumonia caused by commensal oral streptococci by inducing neutrophilic dysfunction in mixed infection. Products of the type IX secretion system should be investigated as novel targets independent of reported virulence factors.

DOI： 10.1093/infdis/jiaf278

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Language：English   Publisher：(一社)日本内科学会  

成人1000例から日本の年齢・性別分布に合わせて抽出した229例を対象に、気管支喘息(BA)、咳喘息(CVA)、慢性閉塞性肺疾患(COPD)、喘息-COPDオーバーラップ(ACO)の有病率と患者自身の疾患認識との一致度について検討した。対象は2014年7月～2017年7月に全身麻酔手術予定で呼吸機能検査を受けた患者229例(平均57.5±16.1歳、男性111例)であった。有病率はBA 10.0%(23例、うちCVA 2例、ACO 6例)、CVA 0.9%、ACO 2.6%、COPD 11.8%(27例、うちACO 6例)であった。喘息関連疾患(BA/CVA/ACO)の自己認識は感度1.00、特異度0.995、κ係数0.976と高い一致を示した。自己申告で喘息関連疾患ありと回答した24例中23例が医学的に確認され、自己申告なしの205例はいずれも喘息関連疾患を持たなかった。COPD関連疾患(COPD/ACO)の自己認識は感度0.481、特異度1.00、κ係数0.621と低く、COPD/ACO 27例中14例(52%)が自己認識を欠いていた。ACOの有病率は喘息例の28.6%、COPD例の22.2%であったが、自己認識としてACOと回答した患者は少なく、特にBAと自己認識している患者の一部はCOPDを認識していなかった。

Language：Japanese   Publisher：Clinical Therapeutics  

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with a poor prognosis. Nintedanib, an antifibrotic agent, has been shown in clinical trials to slow the decline in forced vital capacity (FVC) and reduce acute exacerbations (AE-IPF). Long-term studies confirm its continued effectiveness, though side effects like diarrhea may affect adherence. Despite real-world data supporting nintedanib's benefits, no prospective study has assessed its efficacy in early-stage IPF. This study evaluated the efficacy, safety, and tolerability of nintedanib in patients with early-stage IPF to assess its effectiveness outside randomized control trials. Methods: A 1-year interim analysis of a prospective, multicenter observational study was conducted in Kyushu and Okinawa, Japan. This study included 215 patients with early-stage IPF (stage I/II per the Japanese IPF severity system) who were followed up for 52 weeks. Changes in FVC and diffusion capacity of carbon monoxide (DLco); incidence of adverse events, acute exacerbations, and death; and factors associated with FVC decline and nintedanib discontinuation were evaluated. Results: The percentage of predicted FVC (%FVC) remained stable, from 83.2% at baseline to 83.7% at 52 weeks, while %DLco decreased from 70.8% to 64.2%. Incidences of acute exacerbation and death were both 4.7%. Nintedanib was discontinued due to adverse events in 21.9% of the patients. Risk factors for FVC decline (>5%) included female sex, GAP stage II/III, low oxygen saturation (SpO<inf>2</inf>) in the 6-minute walk test (6 MWT), and elevated biomarkers (KL-6). Significant factors for nintedanib discontinuation were advanced age, modified Medical Research Council (mMRC) grade I or higher, GAP stage II/III, low %FVC, low SpO<inf>2</inf> in the 6 MWT, short 6 MWT distance, and low albumin levels. Conclusion: The findings of this interim analysis indicate that nintedanib has good efficacy, safety, and tolerability for early-stage IPF in real-world settings, outside randomized control trials.

DOI： 10.1016/j.clinthera.2025.05.007

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.resinv.2025.04.007

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Language：English   Publishing type：Research paper (scientific journal)  

Herein, we report a case of peritoneal dialysis (PD)-related peritonitis caused by Staphylococcus caprae (S. caprae). An 88-year-old man who had been receiving PD presented with cloudy effluent and an elevated dialysate white blood cell (WBC) count of 800/μL. He was diagnosed with PD-related peritonitis and treated with intraperitoneal cefazolin and ceftazidime, which promptly cleared the effluent by day 3 and reduced the WBC count in the dialysate to 0/μL by day 5. Culturing of the effluent identified S. caprae (methicillin-resistant coagulase-negative Staphylococcus), so the antibiotic regimen was switched to intraperitoneal vancomycin. The infection resolved without recurrence, and the patient was discharged on day 17 of his hospitalization without requiring catheter removal. Although S. caprae has been implicated in infections of various organs, reports of PD-related peritonitis caused by this bacterium are rare in the literature. This case suggests that S. caprae-related PD peritonitis responds well to antibiotic therapy with intraperitoneal vancomycin and that patients with this infection have a generally favorable prognosis.

DOI： 10.7759/cureus.88870

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Language：English   Publisher：エルゼビア・ジャパン(株)  

症例は50歳女性で、慢性湿性咳嗽を呈しており、慢性副鼻腔炎と中耳感染を原因とする両側性難聴の既往を有し、28歳時にび漫性汎細気管支炎と診断され低用量マクロライド治療を受けていた。1年前、健診での胸部X線検査で異常陰影を指摘されたため近医を受診し、マクロライド治療を再開されたものの効果は得られず、原発性線毛運動障害(PCD)疑いにて当院を紹介された。両親が血族婚であることが判明し、受診時のバイタルサインは体温36.7℃、脈拍数69/分、血圧142/83mmHg、呼吸数18/分を示し、身体診察では喀痰を伴う咳嗽、両肺の水泡音、ばち状指を認め、原発性線毛運動障害評価スコアは4点、胸部X線と高解像度CTにて気管支拡張症と両肺の粒状陰影を検出し、副鼻腔CTで左前頭洞、上顎洞、蝶形骨洞、篩骨洞に液体貯留と粘膜肥厚を認めた。肺機能検査の結果、努力性呼気1秒量は0.72L、呼気中一酸化窒素濃度は低値を示しPCDに矛盾しない所見であった。遺伝子検査を行った結果、RSPH4A遺伝子にホモ接合性ミスセンス変異(NM_001010892.3), c.1484C>A(p.Thr495Asn)が検出された。

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

2011年7月～2012年6月に単一施設で90日以上の血液透析を受けた成人患者339例(中央値67歳)を対象とする後ろ向き観察研究を行い、グラスゴー予後スコア(GPS)、修正GPS(mGPS)、高感度mGPS(HS-mGPS)と全死亡との関連性を評価した。観察期間中(2011年7月～2021年3月)に221例(65.2%)が死亡した。GPSについては、スコアの上昇に伴って生存率が低下したが、mGPSおよびHS-mGPSではスコアと生存率との関連性を認めなかった。Cox比例ハザードモデルにおいて、GPSではスコア0の患者に比べてスコア1およびスコア2の患者では全死亡リスクが有意に上昇したが(ハザード比はそれぞれ1.76、2.87)、mGPSおよびHS-mGPSでは有意な相関を認めなかった。GPSはmGPSおよびHS-mGPSに比べて明確に予後不良リスクの患者を分類することが示された。

Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jiac.2025.102695

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Language：English   Publisher：エルゼビア・ジャパン(株)  

COVID-19に対する2回目のmRNAワクチンを接種した非感染者138例(男性84例、女性54例、年齢20～99歳)を対象に、液性および細胞性免疫反応を調査した。接種したmRNAワクチンはBNT162B2が135例、mRNA-1273が3例であった。液性免疫はIgG抗体の抗体価を接種後6ヵ月まで経時的に測定した。細胞性免疫反応はインターフェロン-γ(IFN-γ)の産生量を定量化して評価した。被験者を70歳未満群58例と70歳以上群80例に分類した。IgG抗体価は70歳以上群の方が有意に低かった。また両群とも接種後6ヵ月のIgG抗体価は接種後3ヵ月より有意に低く、経時的に有意な低下を認めた。血清IFN-γは接種後3ヵ月と6ヵ月の間に有意差はなく、経時的な変化は見られなかった。多変量解析でIgG抗体価は年齢および血清アルブミンと有意に関連した。血清IFN-γはCD4陽性T細胞の発現および全身状態の指標であるECOGのパフォーマンスステータスと有意に関連した。

Language：English   Publisher：エルゼビア・ジャパン(株)  

新型コロナウイルス感染症(COVID-19)の症状が12週間以上持続する長期COVIDについて、オミクロン株流行中の発生率と危険因子について検討した。2022年7月30日～2023年12月31日に14の参加施設で軽症COVID-19と診断された18歳以上の外来患者を対象にオンライン調査を実施した。発症から4、12、24週時に調査を行った。主要評価項目は発症から12週時に認める長期COVID症状[疲労、呼吸器症状(呼吸困難、咳嗽)、神経症状(味覚障害、嗅覚障害、記憶障害)、精神症状(不眠症、抑うつ)、疼痛(筋肉痛、関節痛)、脱毛]とした。発症から4週時に回答が得られた246症例(女性70.3%、年齢中央値39.5歳)を解析した。発症から12週間以内に、214例中76症例(35.5%)で長期COVID症状を認めた。ロジスティック回帰分析の結果、年齢(40歳以上)が呼吸器症状(オッズ比:3.80、95%CI:1.67～8.65)と神経症状(同4.53、1.84～11.13)のリスク増加と有意に関連した。抗ウイルス薬の使用は、呼吸器症状のリスク低下と関連した(同0.31、0.11～0.93)。以上より、40歳以上の軽症COVID-19患者は長期COVIDを発症するリスクが高く、抗ウイルス薬が呼吸器症状の管理と重症度軽減に有益な可能性が示唆された。

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.resinv.2025.02.008

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/kidneydial5020015

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.7759/cureus.81923

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Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Broad-spectrum antimicrobials are commonly administered for community-acquired pneumonia (CAP); however, unnecessary administration may cause adverse events and poor outcomes. This study aimed to understand the impact of broad-spectrum anti-pseudomonal β-lactam use on clinical outcomes and healthcare resource utilization (HCRU) in inpatients with CAP and a low risk of drug-resistant pathogens (DRPs). METHODS: This historical cohort study reviewed Japan's hospital claims database (January to December of 2018) and included inpatients aged ≥ 20 years who received intravenous antimicrobial therapy for CAP. Those with high DRP risk were excluded. According to the initial antimicrobial regimen, patients were divided into broad-spectrum (anti-pseudomonal β-lactam therapy) and narrow-spectrum (non-anti-pseudomonal β-lactam therapy) groups. This study evaluated 30-day hospital mortality as a primary outcome using inverse probability of treatment weighting (IPTW) to adjust for differences between both groups and HCRU as an exploratory analysis. RESULTS: A total of 15,617 patients were analyzed (2627 in the broad-spectrum group and 12,990 in the narrow-spectrum group). In the broad-spectrum group, the 30-day mortality rate was 10.6%, which was higher than that in the narrow-spectrum group (5.3%). Furthermore, it was associated with an increased 30-day mortality compared with the narrow-spectrum group after IPTW (adjusted odds ratio, 1.77; 95% confidence interval, 1.52-2.06; p < 0.001). The mean inpatient cost was USD 6139 and USD 5184 for the broad- and narrow-spectrum groups, respectively. CONCLUSIONS: The initial use of anti-pseudomonal β-lactams for CAP with low DRP risk is associated with poor outcomes, including death and high HCRU. Thus, initial antimicrobials should be judiciously selected for CAP management.

DOI： 10.1007/s40121-025-01142-1

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Language：English   Publishing type：Research paper (scientific journal)  

This case highlights the possibility that Immunoglobulin G4-related disease (IgG4-RD) lesions can also occur in the sternoclavicular joint. If a neoplastic lesion is found in the sternoclavicular joint, a biopsy should be attempted to diagnose IgG4-RD as a differential.

DOI： 10.1002/ccr3.70366

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

Introduction

Usefulness of the Glasgow prognostic score (GPS), modified GPS (mGPS), and high‐sensitivity mGPS (HS‐mGPS) in the prognosis of patients undergoing hemodialysis remains unclear. This study aimed to investigate this.

Methods

The GPS, mGPS, and HS‐mGPS were calculated retrospectively in 339 patients undergoing hemodialysis; their association with all‐cause mortality was analyzed using the Kaplan–Meier method and Cox proportional hazards models.

Results

Survival rates decreased according to the GPS (0, 1, and 2), but were similar between the mGPS and HS‐mGPS. In the multivariate Cox proportional hazards model, the GPS, not the mGPS or HS‐mGPS, was associated with a higher risk of all‐cause mortality in patients with scores 1 (hazard ratio [HR]: 1.76, 95% confidence interval [CI]: 1.29–2.42, p = 0.0004) and 2 (HR: 2.87, 95% CI: 1.91–4.32, p &lt; 0.0001) compared with score 0.

Conclusions

The GPS classified patients into poor prognostic risk groups more clearly than other scores.

DOI： 10.1111/1744-9987.70014

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

Atrial fibrillation (AF) can develop in patients with chronic kidney disease. However, the impact of new-onset AF in patients who are initiated on hemodialysis remains unclear. We categorized 254 patients who were started on hemodialysis into three groups: those with pre-existing AF, those with new-onset AF, and those without AF. Statistical analyses were performed to evaluate the associations between patient characteristics and survival outcomes. AF was observed in 42 patients (16.5%), of whom 19 (7.5%) had pre-existing AF and 23 (9.1%) developed new-onset AF at the initiation of hemodialysis. Multivariate logistic regression models showed that only low serum albumin levels were associated with AF (P = 0.04). Age- and other factors-adjusted multivariable Cox regression models indicated that AF, particularly pre-existing AF, was an independent risk factor for death after dialysis initiation (hazard ratio [HR]: 2.28, 95% confidence interval [CI]: 1.39–3.74, P = 0.001; HR: 3.05, 95% CI: 1.64–5.66, P = 0.004, respectively). However, new-onset AF was not significantly associated with mortality (HR: 1.43, 95% CI: 0.74–2.78, P = 0.28). These findings suggest that pre-existing AF before hemodialysis initiation has a crucial impact on patient prognosis.

DOI： 10.1371/journal.pone.0320336

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：Annals of the American Thoracic Society  

Rationale: Accurate prognostic awareness (PA) and knowledge of the disease are critical for decision-making regarding treatment options, advance care planning, and end-of-life care. However, they have not been investigated in patients with interstitial lung disease (ILD). Objectives: To determine the prevalence of patients with ILD who have accurate PA and/or knowledge of acute exacerbation and whether accurate PA is associated with end-of-life medical interventions and quality of dying and death. Methods: Through a nationwide bereavement survey, we examined the prevalence of accurate PA and knowledge of acute exacerbation (AE) in patients with ILD who died in acute general hospitals between January 2018 and February 2020. Patients’ PA and knowledge were assessed from the perspective of the bereaved. We also quantified the quality of dying and death from the perspective of the bereaved using three scales—the Good Death Inventory, the Quality of Dying and Death questionnaire, and the single-item Quality of Dying and Death overall score—and obtained information on end-of-life interventions from the electronic medical record. We examined the associations of accurate PA with end-of-life interventions and quality of dying and death. Results: A total of 296 patients whose caregivers completed questionnaires were analyzed. One hundred sixty-three patients (55.1%; 95% confidence interval [CI], 49.2–60.8%) who died of ILD had accurate PA, and 138 (46.9%; 95% CI, 41.1–52.8%) recognized that their disease could have AE. Multivariate regression analysis showed that accurate PA was associated with significantly fewer intensive care unit deaths (odds ratio, 0.28; 95% CI, 0.10–0.82; P = 0.02). Patients with accurate PA had better quality of dying and death on all three scales. Conclusions: Approximately half of the patients who died of ILD did not recognize that their disease could lead to death or AE. The lower number of intensive care unit deaths and better quality of dying and death in patients with accurate PA suggest the potential benefits of obtaining accurate PA in patients with ILD.

DOI： 10.1513/AnnalsATS.202405-495OC

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AND OBJECTIVE: For treating community-acquired pneumonia (CAP) in adults, early switching from injectable to oral antimicrobials (switch therapy) is accepted once the clinical course is favorable. Lascufloxacin (LSFX) is a quinolone antibacterial agent, available in intravenous and oral formulations, demonstrating antibacterial activity against a relatively broad spectrum of community-onset pneumonia (COP). No switch therapy using the same drug from injectable to oral antimicrobials has been reported; therefore, we conducted the study to confirm the efficacy and safety of the switch therapy using LSFX. METHOD: We conducted an open-label, uncontrolled, multicenter study across 16 hospitals from April 2023 to February 2024 to evaluate the efficacy and safety of LSFX switch therapy against mild-to-moderate COP. Once the switch criteria were fulfilled on days 3-5, switch therapy was initiated. The primary endpoint was the cure rate at the time of test of cure (TOC). Secondary endpoints included the proportion of patients receiving switch therapy, clinical efficacy at the end of treatment (EOT), early clinical response, microbiological response at the EOT, and adverse events. The adverse events were collected from the population for the safety analysis set. RESULTS: The median age of the participants was 73 years, and the overall switch therapy implementation rate was 114/120 (95%), aligned with approximately 99/104 (95%) of the switch therapy performed by day three after initiating the therapy. The cure or effective rate was 100/104 (96.2%, 95% confidence interval (CI): 90.44-98.94) at TOC, 101/104 (97.1%, 95% CI: 91.80-99.40) at the early clinical efficacy testing, and 103/104 (99.0%, 95% CI: 94.76-99.98) at EOT. Adverse events related to the study drug were reported in 10.0% of the patients, with hepatic dysfunction as the most common adverse effect. Severe LSFX-induced adverse events were not observed, excluding worsening pneumonia. CONCLUSION: Switch therapy using LSFX presented high efficacy and acceptable safety profiles against mild-to-moderate severity of COP. This strategy of using the same drug in both intravenous and oral formulations is quite innovative. LSFX may potentially emerge as one of the preferred options for treating COP.

DOI： 10.7759/cureus.80404

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Objective The prevalence rates of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are 3%-11% and 8%-16%, respectively, in the general Japanese adult population. Few reports on patients' perceptions of BA, cough variant asthma (CVA), COPD, and asthma and COPD overlap (ACO) are available in Japan, and we aimed to investigate the agreement between the perception and diagnosis of BA and COPD-related diseases. Methods The subjects were 229 datasets matched to the sex and age distribution of the Japanese population of 1,000 adult patients who underwent respiratory function tests and screening for each disease at Nagasaki University Hospital between July 2014 and July 2017. The patients' self-perceptions of diagnosed BA, CVA, COPD, emphysema, chronic bronchitis, and ACO were determined. Results In total, 229 datasets were included in this study. The prevalence of BA was 10.0% (23 cases, including 2 CVA and 6 ACO cases) and 11.8% (27 cases, including 6 ACO cases). The prevalence of ACO was 2.6% (28.6% of BA and 22.2% of COPD), and that of CVA was 0.9% (8.7% of BA). The perception of COPD-related diseases had a much lower sensitivity than that of asthma-related diseases (0.481 vs. 0.995, p<0.0001). Cohen's kappa for asthma-related disease was 0.976, and that for COPD-related disease was 0.621. Conclusion Self-perception of asthma-related disease was adequately high, whereas that of COPD-related disease was low. The prevalence rates of BA, COPD, ACO, and CVA in our study were 10.0%, 11.8%, 2.6%, and 0.9%, respectively. An increase in the perception of COPD may help improve community healthcare for respiratory diseases.

DOI： 10.2169/internalmedicine.4519-24

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DOI： 10.7759/cureus.77248

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Language：English   Publisher：エルゼビア・ジャパン(株)  

症例は63歳女性で、20年前に自己免疫性肺胞蛋白症と診断されていた。診断時の抗GM-CSF(顆粒球マクロファージコロニー刺激因子)抗体値は452U/mLであった。進行性肺線維化に伴う呼吸困難が増悪し、61歳時に生体肺移植術を受けた。10ヵ月後に発熱および呼吸困難が出現し、入院となった。胸部HRCT(高分解能CT)で両肺野にすりガラス陰影と浸潤影をび漫性に認めた。臨床検査でC反応性蛋白質は30mg/dLの高値を呈した。細菌性肺炎と診断し、タゾバクタム・ピペラシリンの静注を開始した。血清中の抗GM-CSF抗体値は93U/mLであった。気管支肺胞洗浄液は乳白色を呈し、PAS染色陽性の無構造物質を認めた。自己免疫性肺胞蛋白症の再発と診断した。その後下気道感染症を発症し、喀痰検査は緑膿菌陽性であった。抗生剤の投与を開始した。呼吸困難は徐々に悪化し、9ヵ月後に肺胞動脈血酸素分圧較差(A-aDO2)は70.2mmHgに達した。全肺洗浄は患者負担が大きいと判断し、サルグラモスチムによるGM-CSF吸入療法を開始した。呼吸困難は徐々に改善し、48週後にA-aDO2は18.3mmHgに低下した。

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BACKGROUND: Mediastinal and subcutaneous emphysema usually result from spontaneous rupture of the alveolar wall. We present an educational case of subcutaneous, mediastinal, and retroperitoneal emphysema discovered during a routine medical check-up resulting from an asymptomatic perforation of the sigmoid diverticulum. CASE PRESENTATION: A 66-year-old man presented to our hospital for his health check-up. A chest X-ray revealed mediastinal emphysema during a physical examination. The patient had no subjective symptoms, fever, or hemodynamic instability. Physical examination revealed a snow grip sensation in the anterior neck but no abdominal tenderness. Blood tests showed an elevated inflammatory response, and a plain chest computed tomography scan revealed subcutaneous emphysema around the neck, as well as mediastinal and retroperitoneal emphysema. The patient was then admitted to the hospital and the patient was treated conservatively. On Day 7 post-admission, the emphysema was mildly relieved. However, on Day 10, the patient developed intestinal obstruction caused by barium. Colonoscopy revealed sigmoid colon perforation. On Day 11, partial resection of the sigmoid colon via laparotomy and colostomy (Hartmann operation) was performed. Postoperative pathology revealed a perforation of the sigmoid colon, which was confirmed to be induced by diverticulitis, as multiple diverticula were simultaneously found in the sigmoid colon. CONCLUSIONS: Even in the absence of abdominal symptoms, retroperitoneal emphysema may develop due to perforation of the sigmoid colon. Therefore, if retroperitoneal emphysema is combined with mediastinal emphysema, evaluation, including abdominal CT, should be performed to identify the cause of emphysema.

DOI： 10.1016/j.rmcr.2025.102229

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：長崎医学会  

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DOI： 10.7759/cureus.74856

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DOI： 10.7759/cureus.74294

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/resp.14752

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Language：Japanese   Publisher：The Physical Society of Japan  

DOI： 10.11316/jpsgaiyo.79.2.0_624

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Language：Japanese   Publisher：The Physical Society of Japan  

DOI： 10.11316/jpsgaiyo.79.1.0_532

CiNii Research

Language：Japanese   Publisher：The Physical Society of Japan  

DOI： 10.11316/jpsgaiyo.79.1.0_533

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Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: This case report presents the successful detection of an EGFR exon 19 deletion using virtual bronchoscopic navigation (VBN) and endobronchial ultrasound with guide sheath (EBUS-GS) brushing, integrated with highly sensitive next-generation sequencing (NGS), even in challenging biopsy scenarios. The growing prevalence of driver gene alterations in non-small cell lung cancer necessitates effective bronchoscopic technology and reliable multiplex gene NGS panels. However, data regarding the optimal bronchoscopic techniques when using highly sensitive NGS panels are limited. Herein, we report a case utilizing VBN-guided EBUS-GS brushing as an exploratory approach to address this challenge. CASE PRESENTATION: A 71-year-old man was evaluated for a band-like lesion near the left pleura during spinal cord infarction. Transbronchial specimens were obtained from lesions invisible on conventional chest radiography and X-ray fluoroscopy using VBN and EBUS-GS brushing. Cytological brushing specimens revealed lung adenocarcinoma, and highly sensitive NGS identified an EGFR exon 19 deletion. He was diagnosed with stage IB disease and underwent radical radiotherapy owing to his fragile condition. If recurrence occurs, the patient will be treated with an EGFR inhibitor. CONCLUSION: VBN-guided EBUS-GS brushing, a minimally invasive approach, combined with highly sensitive NGS has the potential to provide accurate molecular diagnoses to more patients with lung cancer, thereby offering opportunities for personalized treatment. Our findings warrant further investigation to determine optimal bronchoscopic technologies for obtaining tumor specimens.

DOI： 10.1159/000540356

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OBJECTIVES: Little is known about how various treatments impact the progression of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. Here, we compared ILD progression in RA patients treated with Janus kinase inhibitors (JAKi) or biological disease-modifying anti-rheumatic drugs (bDMARDs). In vitro experiments were also performed to evaluate the potential effects of the drugs on epithelial-mesenchymal transition (EMT), a key event in pulmonary fibrosis. METHODS: This retrospective study included 93 RA-ILD patients who initiated treatment with JAKi, tumour necrosis factor inhibitors (TNFi), or abatacept between 2017 and 2020. Worsening ILD was quantified by changes in chest computed tomography (CT) scans between baseline and follow-up (mean 14 months, range 6-51 months). Response to treatment was evaluated using Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR). Expression of the EMT marker N-cadherin in A549 lung cells was assessed by western blotting. RESULTS AND DISCUSSION: Worsening ILD was detected in 19.4% (7/36), 16.7% (5/30), and 22.2% (6/27) of patients treated with JAKi, abatacept, and TNFi, respectively. Multivariate analysis identified female gender (P=0.043) and >10% fibrotic lesions (P=0.015) as significant predictors of worsening ILD. DAS28-ESR-based non-responder status was also significantly associated with worsening ILD (P=0.0085). In vitro, combination treatment with methotrexate and baricitinib significantly impeded EMT progression. Worsening ILD was associated with more extensive fibrotic lesions at baseline and female gender in RA patients treated with JAKi or bDMARDs. JAKi and methotrexate co-treatment may prove beneficial in modifying key events underlying the pathogenesis of RA-ILD.

DOI： 10.3389/fimmu.2024.1501146

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The diagnosis of pulmonary lymphoma using small tissue samples is difficult and often requires surgical procedures; thus, a less invasive sampling method is desirable. Moreover, pulmonary involvement in adult T-cell lymphoma (ATL) is often difficult to diagnose, especially in cases without characteristic flower cells. Here, we present the case of a 78-year-old man, in whom pathological examination of the transbronchial lung biopsy (TBLB) specimen did not reveal malignant findings; therefore, transbronchial lung cryobiopsy (TBLC) in combination with endobronchial ultrasonography (EBUS) was used to diagnose ATL based on the pathological findings. A literature review identified 18 cases of pulmonary lymphomas diagnosed using TBLC. Among the 19 cases, including our own, 16 cases were of B-cell lymphoma (84.2%), and the present case is the first case of ATL diagnosed using TBLC. Eighty percent of the cases underwent a biopsy (more than two samples) of the middle or lower lobe and were diagnosed without major complications. EBUS was used with TBLC in three cases to identify the location of the pulmonary lesions. In the present case, EBUS was also useful for avoiding vascular biopsy. Although large-scale prospective studies are required to establish precise guidelines for diagnosing pulmonary lymphomas using TBLC, our case report and review contributes to a deeper understanding of the diagnosis of rare diseases.

DOI： 10.3390/medicina59112015

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Sarcoidosis is a systemic inflammatory disease characterized by noncaseating epithelioid cell granulomas. However, certain infections can exhibit similar histological findings. We present a case of a 69-year-old man who was initially diagnosed with sarcoidosis and later was confirmed, through 16S rRNA sequencing, to have disseminated Mycobacterium genavense infection. Acid-fast bacteria were detected in the bone marrow biopsy using Ziehl-Neelsen staining, but routine clinical tests did not provide a definitive diagnosis. The patient tested negative for HIV, anti-interferon-gamma antibodies, and genetic immunodeficiency disorders. He was treated with multiple drugs, including aminoglycosides and macrolides, but showed no improvement in fever and pancytopenia. However, these clinical signs responded favorably to steroid therapy. We reviewed 17 Japanese cases of M. genavense infection. All cases were in males; 7/17 (41%) were HIV-negative; and 12/17 (71%) had a decreased CD4 count. Genetic analysis confirmed M. genavense isolation, and macrolides were used universally. Mycobacterium genavense infection is challenging to identify and mimics other systemic inflammatory diseases such as sarcoidosis. There are no standard treatment protocols. Our case report and Japanese case review contribute to understanding this rare disease.

DOI： 10.3390/microorganisms11092145

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Authorship：Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Background

Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has demonstrated effectiveness in treating ovarian, breast, and other cancers, particularly those with specific molecular subtypes including, but not limited to, BRCA1/2 mutations. Consequently, its utilization is expected to increase in the future. For this reason, it is important to acknowledge the potential for adverse events associated with olaparib, including the relatively rare but significant risk of drug-induced interstitial lung disease (DIILD). Since DIILD can lead to fatal outcomes, its early detection is crucial. The dissemination of knowledge regarding DIILD can be facilitated through case reports; however, specific reports of DIILD caused by olaparib have only been published in Japanese. To the best of our knowledge, this is the first report in English of our experience with three cases of DIILD caused by olaparib.

Case presentation

Cases 1, 2, and 3 involved Japanese women with ovarian cancer who had been receiving olaparib at a dose of 600 mg/day. Case 1, a 72-year-old woman who had been on olaparib for 4 months, and case 2, a 51-year-old woman who had been on olaparib for 8 months, reported fever and general malaise. Chest computed tomography (CT) revealed pale ground glass opacity (GGO) similar to hypersensitivity pneumonitis. The severity grade was 2 in both cases. Case 3, a 78-year-old woman who had been on olaparib for 3 weeks, presented with cough and reported dyspnea on exertion. Chest CT revealed non-specific interstitial pneumonia and organizing pneumonia-like shadows. The severity grade was 4. Olaparib was discontinued in all cases. Case 1 received 0.6 mg/kg of prednisolone due to mild hypoxia, while prednisolone was not administered in case 2 due to the absence of hypoxia. Case 3 received steroid pulse therapy due to severe hypoxia. Olaparib administration was not resumed in any patient.

Conclusion

DIILD caused by olaparib in Japan, including the present three cases, commonly presents with GGO, similar to hypersensitivity pneumonitis on chest CT. The prognosis for the majority of patients is favorable; however, there have been instances of severe cases. Early recognition of drug-induced lung injury and further accumulation of cases is important.

DOI： 10.1186/s12890-023-02569-3

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Other Link： https://link.springer.com/article/10.1186/s12890-023-02569-3/fulltext.html

Language：English  

Inhaled liposomal antimicrobials are known to cause hypersensitivity pneumonitis. Amikacin liposome inhalation suspension (ALIS) is a promising novel antimicrobial agent against refractory Mycobacterium avium complex infections. The frequency of drug-induced lung injury caused by ALIS is relatively high. To date, no reports of ALIS-induced organizing pneumonia diagnosed by bronchoscopy are available. We report a case of a 74-year-old female patient presenting with non-tuberculous mycobacterial pulmonary disease (NTM-PD). She was treated with ALIS for refractory NTM-PD. Fifty-nine days after starting ALIS, the patient developed a cough, and her chest radiographs indicated deterioration. She was diagnosed with organizing pneumonia based on pathological findings of the lung tissues obtained by bronchoscopy. After switching from ALIS to amikacin infusion, her organizing pneumonia improved. It is difficult to distinguish between organizing pneumonia and an exacerbation of NTM-PD based on chest radiography alone. Therefore, it is essential to perform an active bronchoscopy for diagnosis.

DOI： 10.1016/j.jiac.2023.04.013

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A 65-year-old Japanese woman repeatedly withdrew and resumed antibiotics against pulmonary non-tuberculous mycobacterial infection caused by Mycobacterium intracellulare for more than 10 years. Although she continued to take medications, her respiratory symptoms and chest computed tomography indicated an enlarged infiltrative shadow in the lingular segment of the left lung that gradually worsened over the course of a year or more. Bronchoscopy was performed and mycobacterial culture of the bronchial lavage fluid was negative, whereas Exophiala dermatitidis was detected. After administration of oral voriconazole was initiated, the productive cough and infiltrative shadow resolved. There are no characteristic physical or imaging findings of E. dermatitidis, and it often mimics other chronic respiratory infections. Thus, when confronting refractory non-tuberculous mycobacterial cases, it might be better to assume other pathogenic microorganisms, including E. dermatitidis, and actively perform bronchoscopy.

DOI： 10.1016/j.jiac.2023.03.010

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Pulmonary nodular lymphoid hyperplasia (PNLH) is a very rare disease, and it is difficult to diagnose PNLH and distinguish it from mucosa-associated lymphoid tissue (MALT) lymphoma. In addition, information on bronchoalveolar lavage fluid (BALF) analyses is lacking. We herein report a 36-year-old Japanese woman diagnosed with PLNH by a surgical biopsy and analysis of BALF. The BALF showed an increase in B-cell marker-positive lymphocytes, normal patterns of B-cell clonality, mucosa-associated lymphoid tissue 1 gene, and immunoglobulin heavy chain at 14q32 translocations. We also reviewed Japanese cases of PNLH described in Japanese or English to explore the characteristics of such cases.

DOI： 10.2169/internalmedicine.9310-21

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Authorship：Corresponding author   Language：English  

A 63-year-old Japanese woman with multiple cysts in both lungs on chest computed tomography (CT) was referred to our hospital after a thorough examination, including a transbronchial lung biopsy (TBLB), failed to provide a diagnosis. Based on the findings on chest CT and pathological examination of the bronchoalveolar lavage fluid and transbronchial lung cryobiopsy (TBLC) specimen, the patient was diagnosed with pulmonary Langerhans cell histiocytosis (PLCH). TBLC may replace TBLB as the main diagnostic technique for PLCH, although further studies are required to determine the usefulness of TBLC for the diagnosis of PLCH.

DOI： 10.1016/j.rmcr.2023.101928

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UNLABELLED: The accuracy of transbronchial lung cryobiopsy (TBLC) in each disease for pathological and multidisciplinary discussion (MDD) diagnosis is not yet established. METHOD: We investigated 431 patients who were classified by MDD diagnosis and were grouped into the disease categories. For each category or disease, we used TBLC samples to calculate the sensitivities of the pathological diagnosis compared with MDD diagnoses. Further, we compared these sensitivities to pathological diagnoses with all clinical/radiological information. RESULT: The sensitivity for diagnosing idiopathic interstitial pneumonia (IIPs) with TBLC was higher than connective tissue disease associated ILD (CTD-ILD). Idiopathic nonspecific interstitial pneumonia (iNSIP), fibrotic hypersensitivity pneumonitis, and some CTD-ILDs were diagnosed with lower sensitivities compared to IPF. The sensitivity of pathological diagnosis with all clinical/radiological information in IPF was higher than in iNSIP, but not significantly different from other diseases. The overall sensitivity of the pathological diagnosis with clinical/radiological information was 69.0%, significantly higher than without clinical/radiological information. CONCLUSION: The sensitivity of pathological diagnosis with TBLC was low for some diseases except IPF. The addition of all clinical/radiological information increased the sensitivity of pathology diagnosis by TBLC, which was no less sensitive than IPF for all diseases except iNSIP.

DOI： 10.1038/s41598-022-26510-6

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BACKGROUND: The lung cancer biopsy specimens obtained by endobronchial ultrasound-guide sheath (EBUS-GS) trans lung biopsy occasionally do not contain cancer cells. It is a problem that there is a possibility that they may not contain cancer cells. AIM OF THE STUDY: To investigate the proportion of biopsy specimens containing cancer cells in total biopsy specimens. MATERIALS & METHODS: Patients with lung cancer diagnosed by EBUS-GS were selected. The primary end point was the proportion of specimens containing tumors in the total specimens obtained by EBUS-GS. RESULTS: Twenty-six patients were investigated. The percentage of specimens containing cancer cells in the total specimens was 79.0%. CONCLUSION: The proportion of biopsy specimens containing cancer cell to all biopsy specimens by EBUS-GS was high, but not 100%.

DOI： 10.2217/lmt-2022-0001

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

A 36-year-old Japanese man presented with cavities and nodular shadows in the lower lobes of his lungs and osteolytic lesions in the thoracic spine. He was diagnosed with multisystem Langerhans cell histiocytosis (LCH). Three years earlier, he had been noted to have small cavities and granular lesions noted in the upper lobes of his lungs, which later improved with smoking cessation. It was likely that his single-system pulmonary LCH (PLCH) progressed to multisystem LCH despite smoking cessation. Relapse or progression may occur in cases where PLCH lesions improve after smoking cessation. Thus, close follow-up is vital.

DOI： 10.2169/internalmedicine.0139-22

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Language：Japanese   Publisher：長崎医学会  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s10916-022-01811-5

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Language：Japanese   Publisher：長崎医学会  

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A 65-year-old Japanese man with interstitial pneumonia demonstrated honeycomb lung with thickened walls on chest high-resolution computed tomography (HRCT) and predominance of neutrophils in the cell fraction of the bronchoalveolar lavage fluid. Although there were no centrilobular nodular or branching shadows on chest HRCT suggestive of diffuse panbronchiolitis, he exhibited sinusitis and had the HLA-B54 antigen. With long-term macrolide therapy, the cough and sputum production markedly improved, wall thickening of the honeycomb lung on chest HRCT decreased, and the forced vital capacity increased. Confirming the presence of HLA-B54 antigen may help determine the indication for long-term macrolide therapy in interstitial pneumonia patients.

DOI： 10.2169/internalmedicine.9304-21

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies are myositis-specific autoantibodies that have been identified in a subset of patients with interstitial pneumonia who do not present with dermatomyositis or polymyositis. Anti-ARS antibody-positive interstitial pneumonia is commonly treated with steroids or immunosuppressive agents and is usually responsive to these therapies. Here, we present in detail a case in which respiratory failure of a patient diagnosed with anti-ARS antibody-positive interstitial pneumonia was exacerbated by treatment with steroids and immunosuppressive agents. Further examination revealed misdiagnosis of this patient and a subsequent diagnosis of autoimmune pulmonary alveolar proteinosis. CASE PRESENTATION: A 66-year-old man presented to the hospital with dyspnea on exertion, which resulted in the detection of interstitial pneumonia. Serum anti-ARS antibodies were detected; however, there were no other findings suggestive of myositis. Pulmonary alveolar proteinosis (PAP) was suspected based on the marked increase in serum KL-6 and chest computed tomography findings. The bronchoalveolar lavage revealed no milky changes in the lavage fluid. After treatment with steroids and initiation of immunosuppressive agents for anti-ARS antibody-positive interstitial pneumonia, respiratory failure and chest imaging findings showed worsening of the condition. Bronchoscopy was repeated, and milk-like alveolar lavage fluid was collected; serum anti-granulocyte macrophage colony-stimulating factor antibody was identified. Steroids and immunosuppressive agents were gradually tapered and discontinued, and the patient's condition stabilized after repeated alveolar lavage under general anesthesia. CONCLUSION: Due to similar presentation, PAP can be misdiagnosed as interstitial pneumonia. If pulmonary lesions due to interstitial pneumonia are exacerbated by immunosuppressive treatment, physicians should reconsider the diagnosis and include PAP in the differential diagnosis.

DOI： 10.1186/s12890-022-01909-z

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.resinv.2022.02.002

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Language：Japanese   Publisher：Japanese Journal of Infectious Diseases  

Human coronaviruses (HCoVs) are distributed globally and they cause a range of respiratory symptoms. Since HCoV infection usually causes mild upper respiratory tract disease and currently has no specific therapy, there are limited reports on its features, especially in adults. We aimed to evaluate the features of HCoV infections in clinical settings. Adult patients with respiratory symptoms from October 2014 to September 2019 at Nagasaki Genbaku Isahaya Hospital were enrolled. Multiplex reverse transcription-polymerase chain reaction as performed for 15 viruses, including HCoVs, and eight bacterial species on the patients’ respiratory specimens. A total of 121 cases were recruited with HKU1, OC43, 229E, and NL63 strains in 80, 21, 12, and 11 cases, respectively. The percentage of HCoV-infected patients peaked in winter (47.5%). Symptoms of fever (69.4%), cough (47.9%), and comorbidities of asthma/cough variant asthma (34.7%) were frequently observed. Lymphocytopenia and increased C-reactive protein levels were observed in laboratory tests. Co-infection with other viruses was identified in 38.8% of the cases. In the repeat-positive cases, 42% were repeat positive within 100 days. HCoV-infected patients showed winter seasonality with a high frequency of comorbidity with asthma and co-infections. Re-infection within an early period was suspected, but further consideration is required.

DOI： 10.7883/yoken.JJID.2021.250

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Authorship：Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/rcr2.880

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.5588/ijtld.21.0319

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1136/bmjopen-2021-053325

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1016/j.resinv.2021.08.006

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Reduced sensitivity of tuberculosis (TB) interferon-γ release assays (IGRAs) among the elderly has been reported, which is presumably due to diminished immune function. We evaluated the clinical performance of QuantiFERON®-TB Gold plus (QFT-Plus) compared with QuantiFERON®-TB Gold In-Tube (QFT-GIT) and T-Spot®.TB (T-SPOT) in the elderly. METHODS: Blood samples for all three IGRAs were drawn at the same time from all the participants. Both CD4 and CD8 T-cell counts in patients' peripheral blood were also measured. RESULTS: A total of 142 active pulmonary TB patients (median age: 84, interquartile range; 76-89 years) were recruited. The sensitivities of the tested IGRAs (excluding invalid/indeterminate cases) were as follows: QFT-Plus, 93.6%; QFT-GIT, 91.4%; and T-SPOT 68.1%. QFT-Plus displayed significantly higher sensitivity than T-SPOT (p < 0.00001). All three IGRAs exhibited the same specificity (100%), as assessed using blood samples from healthy, low TB-risk individuals (n = 118; median age: 39, IQR; 32-47 years). Positivity in 43 active TB patients with CD4 T-cell counts <200/μL, 39 of whom were ≥80 years of age, was as follows: QFT-Plus, 83.7%; QFT-GIT, 74.4%; and T-SPOT, 58.1%. The difference between TB2-TB1 of the QFT-Plus assay was statistically correlated with CD8 but not CD4 T-cell counts in blood (r = 0.193, p = 0.0298). CONCLUSIONS: QFT-Plus showed high performance in the detection of TB infection in patients irrespective of their advanced age (≥80 years) or lower CD4 counts. QFT-Plus can be useful for the diagnosis of TB infection in all patients, including those who are elderly and/or immunocompromised.

DOI： 10.1016/j.jiac.2021.08.016

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.3390/jcm10163552

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Language：Japanese   Publisher：長崎大学医学部保健学科  

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J04983&link_issn=&doc_id=20210819400008&doc_link_id=http%3A%2F%2Fhdl.handle.net%2F10069%2F00040986&url=http%3A%2F%2Fhdl.handle.net%2F10069%2F00040986&type=%92%B7%8D%E8%91%E5%8Aw%81F%92%B7%8D%E8%91%E5%8Aw_%8Aw%8Fp%8C%A4%8B%86%90%AC%89%CA%83%8A%83%7C%83W%83g%83%8A%28NAOSITE%29&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80040_3.gif

Language：Japanese   Publisher：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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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/1759-7714.13890

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/ccr3.3628

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/1759-7714.13756

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Authorship：Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.rmcr.2021.101523

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