Publications by authors named "Noboru Hattori"

Immune checkpoint inhibitors (ICIs) have been approved for treating various cancers; however, they can cause immune-related adverse events. Generally, ICIs are not associated with an increased risk of infection, however, several reports demonstrated infections caused by nontuberculous mycobacterium (NTM) during ICI therapy. Here, we report a case of NTM shoulder arthritis with acute exacerbation immediately after ICI initiation.

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Background: Sensitization to mucus plugs, and bacterial colonization may coexist and relate to a refractory phenotype during follow-up in asthma with bronchiectasis and allergic bronchopulmonary aspergillosis (ABPA).

Objective: This study aimed to clarify the features of -sensitized refractory asthma with bronchiectasis and determine the refractory phenotype in this population and ABPA.

Methods: This study included cases of the oldest available -specific IgE data and chest computed tomography images from a nationwide survey of refractory asthma with bronchiectasis.

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BackgroundWith global aging, especially in Asia, preventing pneumonia among seniors is vital. The necessity of introducing pneumococcal vaccines among the elderly has been highlighted but there is a paucity of community-based real-world evidence on their effect. Sera Town in Hiroshima Prefecture, a super-aged community, launched a distinctive pneumococcal vaccination support project for elderly residents and conducted a 5-year follow-up survey.

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Background: The receptor for advanced glycation end product (RAGE) is a transmembrane receptor accelerating a pro-inflammatory signal. RAGE signalling is promoted by decreased soluble isoform of RAGE (sRAGE), which is a decoy receptor for RAGE ligands, and RAGE SNP rs2070600 minor allele. In Caucasian and Japanese cohorts, low circulatory sRAGE levels and presence of the minor allele are associated with poor survival of idiopathic pulmonary fibrosis (IPF) and increased disease susceptibility to interstitial lung disease, respectively.

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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.

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Introduction: There have been only a few cases showing the efficacy of pembrolizumab on granulocyte-colonystimulating factor (G-CSF)-producing non-small-cell lung cancer (NSCLC) with high programmed cell death ligand 1 (PD-L1) expression. Herein, we report the first case showing the efficacy of pembrolizumab for G-CSF-producing NSCLC with high PD-L1 expression, although the patient had factors indicative of poor pembrolizumab efficacy, such as poor performance status (PS) due to the tumor-induced inflammation and corticosteroids administration.

Case Presentation: A 77-year-old woman was diagnosed with G-CSF-producing NSCLC-not otherwise specified, classified as clinical stage IVB, T2N3M1c.

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Article Synopsis
  • The study investigates the effectiveness of immune checkpoint inhibitors (ICI) for non-small cell lung cancer (NSCLC) patients, particularly comparing those with brain metastases (BM) to those without.
  • It analyzes data from 240 patients, finding no major overall survival differences between the two groups, but identifies a significant survival disadvantage for patients with BM among those with high PD-L1 expression (≥50%).
  • The conclusion suggests that while ICI is generally effective for both groups, patients with BM and high PD-L1 levels may have poorer outcomes compared to their counterparts without BM.
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A 63-year-old Japanese female presented with fever. Computed tomography showed multiple nodules in both lungs. Corticosteroids and antibiotics were administered to treat suspected organizing and bacterial pneumonia, resulting in no improvement and respiratory failure worsened.

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  • Bone marrow-derived cells with high aldehyde dehydrogenase (ALDH) activity have shown promise for treating diseases in animal models, but clinical trials have not confirmed this success, prompting the need to explore optimal conditions for their efficacy.
  • In a study using a mouse model of pulmonary fibrosis, it was found that transferring female-derived, lineage-negative ALDH cells improved fibrosis significantly more than male-derived or lineage-positive cells, especially when administered during the fibrotic phase of the disease.
  • The improved effects of female-derived ALDH cells were linked to their greater resistance to oxidative stress, suggesting that sex-based differences should be considered when developing ALDH cell therapies for clinical use.
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  • - The study explored the causal relationship between primary aldosteronism (PA) and cardiovascular diseases such as coronary artery disease (CAD), congestive heart failure (CHF), and stroke, using a cross-ancestry meta-analysis of genetic data.
  • - The researchers identified 7 genetic loci linked to PA risk through an extensive analysis of East Asian and European ancestry samples, finding increased risk estimates for CAD, CHF, and stroke among individuals with PA.
  • - The findings suggest that PA significantly raises the risk of various cardiovascular issues, underlining the importance of early screening and intervention for individuals at risk.
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Background: NY-ESO-1 and XAGE1 cancer/testis antigens elicit humoral and cellular immune responses in NSCLC patients. We aimed to predict clinical benefit with ICI monotherapy, using an automated immunoassay of NY-ESO-1/XAGE1 antibodies (Abs).

Methods: This study enrolled 99 NSCLC patients who received nivolumab after chemotherapy, including 21 patients harboring EGFR, ALK, or KRAS alterations.

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  • High-resolution computed tomography (HRCT) is essential for diagnosing Idiopathic Pulmonary Fibrosis (IPF), but it can be confused with other interstitial lung diseases (ILDs) due to similar radiologic patterns.
  • Researchers used mass spectrometry to analyze plasma extracellular vesicles (EVs) from different patient groups, identifying a five-protein signature that distinguishes IPF from other ILDs and healthy individuals.
  • The study validated these biomarkers in independent cohorts, showing high accuracy but emphasizes the need for further large-scale studies to confirm their clinical application.
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Background: There is no established standard 3 line treatment for patients with advanced non-small cell lung cancer (NSCLC). Although cytotoxic chemotherapeutic agents that are not used as 1 or 2 line treatment are administrated as 3 line treatment, their anti-tumor efficacy is insufficient. Anti-programmed death ligand-1 (PD-L1)/programmed death-1 (PD1) treatment is more effective and less toxic than chemotherapy in anti-PD-L1/PD-1 treatment-naïve patients with NSCLC.

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  • A 71-year-old man experienced difficulty breathing during exertion and was diagnosed with pleural mesothelioma after a CT scan showed nodular lesions on his pleura.
  • A thoracoscopic biopsy confirmed the epithelioid type of mesothelioma, and initial chemotherapy treatment was started.
  • The patient showed a decrease in serum KL-6 levels, which correlated with tumor shrinkage, marking the first report of KL-6 being produced by the tumor cells in this type of cancer.
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Pathogen identification is essential for the treatment of bacterial meningitis. However, cerebrospinal fluid (CSF) culture tests are often negative when antimicrobial agents are administered before CSF is collected. Therefore, it is necessary to improve the culturing process for such samples.

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  • Lipocalin-2 (LCN2) is increased in patients with idiopathic pulmonary fibrosis (IPF) during episodes of acute exacerbation, indicating its potential as a systemic biomarker.
  • The study showed that elevated serum LCN2 levels predict poor survival in IPF patients experiencing acute exacerbations, and higher LCN2 levels correlate with worsened lung injury in a mouse model.
  • LCN2 appears to play a protective role in lung injury by modulating oxidative stress responses, as indicated by differences in outcomes between normal and LCN2-knockout mice following bleomycin treatment.*
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  • - S100A9 is a protein linked to inflammation and fibrosis, and the study explored how paquinimod, which inhibits S100A9, affects lung fibrosis development in a mouse model and its potential prognostic value in patients with idiopathic pulmonary fibrosis (IPF).
  • - In the mouse model, bleomycin increased S100A9 expression in the lungs, and paquinimod treatment successfully reduced lung fibrosis and inflammatory cell counts, indicating its therapeutic potential.
  • - High levels of S100A9 in patient serum and lung fluid were associated with worse survival outcomes in IPF, suggesting that S100A9 could serve as a biomarker for disease prognosis.
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  • Protein-protein interactions (PPIs) are crucial for many biological functions, and understanding them is essential for studying how proteins work.
  • The study proposes a straightforward method to assess PPI using mammalian cells, involving introduction of expression vectors, cell lysis, and protein isolation with an affinity gel.
  • The researchers also suggest using affinity antibodies to confirm PPIs, highlighting the importance of maintaining protein integrity throughout the process for accurate results.
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  • - The study focuses on drug-induced interstitial lung disease (DILD), aiming to identify specific biomarkers to enhance clinical management and improve drug development outcomes.
  • - Researchers discovered that serum levels of kynurenine and quinolinic acid were significantly higher in acute DILD patients compared to other lung disease patients and healthy controls, suggesting these could serve as effective diagnostic markers.
  • - The findings indicate a potential relationship between increased kynurenine levels and inflammation, with experiments showing that certain inflammatory conditions can activate the kynurenine pathway in macrophages, contributing to elevated biomarker levels in DILD.
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  • This study looked at a protein called periostin to see if it could help doctors predict how well patients with a lung disease called idiopathic pulmonary fibrosis (IPF) would do after treatment with a drug named nintedanib.
  • Researchers measured different levels of periostin in 87 patients and compared them to 43 other patients who hadn't been treated with antifibrotic drugs before.
  • They found that higher levels of periostin were linked to better chances of survival and more effectiveness of nintedanib in treating IPF, which might help doctors make better treatment plans in the future.
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Background: The prognosis of patients with lung cancer accompanied by interstitial pneumonia is poorer than that of patients with lung cancer but without interstitial pneumonia. Moreover, the available therapeutic interventions for lung cancer patients with interstitial pneumonia are limited. Therefore, a new treatment strategy for these patients is required.

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  • Small amounts of the EGFR T790M mutation (micro-T790M) can be identified in tissue samples through droplet digital PCR, which might serve as a predictive factor for the effectiveness of EGFR-tyrosine kinase inhibitors (TKIs).
  • The study aimed to clarify the predictive value of micro-T790M for three generations of EGFR-TKIs (1G, 2G, and 3G) by excluding potential false positives in previous analyses.
  • Results showed that micro-T790M-positive patients had a significantly longer time to treatment failure (TTF) with 2G and 3G EGFR-TKIs compared to those receiving 1G, indicating that micro-T790M could
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: Olfactory dysfunction is a clinical sign that is important to detect with coexistent upper airway comorbidities in patients with asthma. This study aimed to investigate the etiology of olfactory dysfunction in patients with asthma and the relationship between fractional exhaled nitric oxide (FeNO) levels. : This study included 47 asthma patients who were evaluated for olfactory dysfunction at Hiroshima University Hospital between 2012 and 2020.

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  • Early detection and management of treatment-related interstitial lung disease (ILD) are crucial for cancer patients.
  • A machine learning algorithm was developed to quantify fine crackles, proving to be more sensitive than chest X-rays in identifying interstitial lung changes.
  • Analysis of two lung cancer patients using this algorithm showed elevated fine crackle quantitative values (FCQV) before the official diagnosis of ILD, suggesting its potential for early diagnosis.
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Background: Nestin, an intermediate filament protein, participates in various pathophysiological processes, including wound healing, angiogenesis, endothelial-mesenchymal transition (EndoMT), and fibrosis. However, the pathophysiological roles of lung nestin-expressing cells remain unclear due to conflicting reports. The objective of this study is to elucidate the characteristics and functions of lung nestin-expressing cells.

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