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Shingo Noguchi,1 Kazuhiro Yatera,1 Tatsuji Kato,2 Yasuo Chojin,2 Yoshihisa Fujino,3 Kentaro Akata,1 Toshinori Kawanami,1 Noriho Sakamoto,4 Hiroshi Mukae4 1Department of Respiratory Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; 2Department of Respiratory Medicine, Tobata Kyoritsu Hospital, Kitakyushu, Japan; 3Department of Preventive Medicine and Community Health, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; 4Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan Introduction: The clinical significance of the number of aspiration risk factors in patients with pneumonia is unknown as yet. In the present study, we clarify the significance of the number of aspiration risk factors for mortality and recurrence in pneumonia patients.Methods: This study included 322 patients hospitalized with pneumonia between December 2014 and June 2016. We investigated associations between the number of aspiration risk factors present (orientation disturbance, bedridden, chronic cerebrovascular disease, dementia, sleeping medications and gastroesophageal disease) and 30-day and 6-month mortality, and pneumonia recurrence within 30 days.Results: Patients were categorized by number of risk factors present into groups of 0–1, 2, 3, and 4 or more. Of a total of 322 patients, 93 (28.9%) had 0–1 risk factors, 112 (34.8%) had 2, 88 (27.3%) had 3, and 29 (9.0%) had 4 or more risk factors. The percentages of patients with recurrence of pneumonia were 13.0%, 33.0%, 43.2%, and 54.2% in the 0–1, 2, 3, and 4 or more risk factor groups, respectively. The percentages of patients with 30-day mortality were 2.2%, 5.4%, 11.4%, and 24.1%, and those of patients with 6-month mortality were 6.6%, 24.5%, 30.7%, and 50.0%, in the 0–1, 2, 3, and 4 or more risk factor groups, respectively.Conclusions: The number of aspiration risk factors was associated with increases in both mortality and recurrence in pneumonia patients. Therefore, in clinical practice, physicians should consider not only the presence of aspiration risks but also the number of aspiration risk factors in these patients. Keywords: aspiration pneumonia, bedridden, dementia, sleeping medications, mortality, recurrence of pneumonia

Keisuke Naito,1 Kei Yamasaki,1 Kazuhiro Yatera,1 Kentaro Akata,1 Shingo Noguchi,1 Toshinori Kawanami,1 Kazumasa Fukuda,2 Takashi Kido,1 Hiroshi Ishimoto,3 Hiroshi Mukae3 1Department of Respiratory Medicine, 2Department of Microbiology, University of Occupational and Environmental Health, Japan, Kitakyushu City, Fukuoka, 3Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki City, Nagasaki, Japan Abstract: Pulmonary emphysema is an important radiological finding in chronic obstructive pulmonary disease patients, but bacteriological differences in pneumonia patients according to the severity of emphysematous changes have not been reported. Therefore, we evaluated the bacteriological incidence in the bronchoalveolar lavage fluid (BALF) of pneumonia patients using cultivation and a culture-independent molecular method. Japanese patients with community-acquired pneumonia (83) and healthcare-associated pneumonia (94) between April 2010 and February 2014 were evaluated. The BALF obtained from pneumonia lesions was evaluated by both cultivation and a molecular method. In the molecular method, ~600 base pairs of bacterial 16S ribosomal RNA genes in the BALF were amplified by polymerase chain reaction, and clone libraries were constructed. The nucleotide sequences of 96 randomly selected colonies were determined, and a homology search was performed to identify the bacterial species. A qualitative radiological evaluation of pulmonary emphysema based on chest computed tomography (CT) images was performed using the Goddard classification. The severity of pulmonary emphysema based on the Goddard classification was none in 47.4% (84/177), mild in 36.2% (64/177), moderate in 10.2% (18/177), and severe in 6.2% (11/177). Using the culture-independent molecular method, Moraxella catarrhalis was significantly more frequently detected in moderate or severe emphysema patients than in patients with no or mild emphysematous changes. The detection rates of Haemophilus influenzae and Pseudomonas aeruginosa were unrelated to the severity of pulmonary emphysematous changes, and Streptococcus species – except for the S. anginosus group and S. pneumoniae – were detected more frequently using the molecular method we used for the BALF of patients with pneumonia than using culture methods. Our findings suggest that M. catarrhalis is more frequently detected in pneumonia patients with moderate or severe emphysema than in those with no or mild emphysematous changes on chest CT. M. catarrhalis may play a major role in patients with pneumonia complicating severe pulmonary emphysema. Keywords: clone library method, chronic obstructive pulmonary disease, Goddard classification, molecular method, microflora, phylotype, Moraxella catarrhalis

Midori Shimada,1,2 Minoru Fukuda,2,3 Masaaki Fukuda,2 Takeshi Kitazaki,2 Kohji Hashiguchi,2 Takaya Ikeda,1 Hiroyuki Yamaguchi,1 Katsumi Nakatomi,1 Kazuto Ashizawa,3 Hiroshi Mukae1 1Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, 2Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Hospital, 3Clinical Oncology Center, Nagasaki University Hospital, Nagasaki, Japan Abstract: A 62-year-old female patient with renal dysfunction and pulmonary adenocarcinoma developed postoperative recurrence and received carboplatin/pemetrexed and maintenance pemetrexed. As an anaplastic lymphoma kinase (ALK) gene translocation was identified, the therapy was changed to crizotinib. However, the patient’s blood creatinine level increased, and her physical status worsened. Alectinib also induced exacerbation of renal dysfunction but was controlled by dose reduction of 140 mg twice daily for 2 weeks treatment and 2 weeks break were repeated, and exhibited a partial response for 16 months. Here, we describe the case in which alectinib treatment had beneficial clinical effects on ALK-positive lung adenocarcinoma, which controlled the adverse renal effects by dose reduction and drug breaks. Keywords: lung cancer, ALK, renal dysfunction, alectinib

Background The Wisteria floribunda agglutinin-positive human Mac-2-binding protein ( WFA+-M2 BP) is a new liver fibrosis glycobiomarker with unique fibrosis-related glyco-alteration. WFA+-M2 BP is also a useful surrogate marker for the risk of developing hepatocellular carcinoma and for the liver functional reserve. Aim To evaluate the diagnostic ability of WFA+-M2 BP for liver fibrosis in the clinical setting and the clinical utility of WFA+-M2 BP for predicting the efficacy of direct-acting anti-viral ( DAA) treatment for chronic hepatitis C patients. Methods The study included 159 genotype 1 hepatitis C patients who received DAA-based treatment (telaprevir or simeprevir) combined with pegylated-interferon alpha plus ribavirin (108 telaprevir- and 51 simeprevir-based triple treatment). The relation between baseline serum WFA+-M2 BP and treatment efficacy was evaluated. Results The serum WFA+-M2 BP level significantly increased with the progress of liver fibrosis. Area under the receiver operating characteristic curve analysis identified 2.17 as the cut-off index ( COI) for WFA+-M2 BP for diagnosing advanced fibrosis. The sustained virological response ( SVR) rate was significantly, negatively correlated with the serum WFA+-M2 BP level. Multiple logistic regression analysis found a low serum WFA+-M2 BP level (<2.17 COI) to be independently associated with SVR (odds ratio, 4.35, P = 0.027). Even for prior nonresponders and patients with the interleukin-28B minor allele or histological advanced fibrosis, treatment outcome was favourable for patients with a low serum WFA+-M2 BP level. Conclusion Serum WFA+-M2 BP is a non-invasive liver fibrosis marker useful for predicting the efficacy of DAA-based triple therapy for chronic hepatitis C patients. [ABSTRACT FROM AUTHOR]

Accumulating evidence has suggested the involvement of HTLV-I in the inflammatory lesions of various organs, including the lung. However, the causal relationship between HTLV-1 and inflammatory responses in the organs remains to be elucidated. In order to evaluate the expression of HTLV-1 and its effects in the lung, we examined the expression of mRNA for the HTLV-l tax/rex gene in fresh bronehoalveolar lavage cells (BALC) and peripheral blood mononuclear cells (PBMC) of 23 seropositive individuals, including six patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), by use of an improved method of reverse transcription-polymerase chain reaction (RT-PCR). The rax/rex mRNA was more frequently detected in BALC than in PBMC. All the HAM/TSP patients and eight of 17 carriers without neurological symptoms showed the expression of taxi/rex mRNA in the BALC. IgM class antibodies to HTLV-1 were preferentially detected in sera of the tax/rex mRNA-positive individuals. The detection of tax/rex mRNA correlated closely with the presence of lymphocytosis accompanied by an elevated proportion of IL-2 receptor-bearing Tcells in the BALC. Our findings indicate the crucial role of viral expression in the inflammatory response in the lung in HTLV-1-infected individuals. [ABSTRACT FROM AUTHOR]

The pathological diagnosis of idiopathic interstitial pneumonias (IIP) by surgical lung biopsy is important for clinical decision-making. However, there is a need to use less invasive biomarkers to differentiate nonspecific interstitial pneumonia (NSIP) from other IIP such as usual interstitial pneumonia (UIP). Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen. HSP47 is increased in various fibrotic diseases. We investigated the autoantibodies to HSP47 in IIPs.~Background~Background~We measured the serum levels of the autoantibodies to HSP47 in 38 patients with various forms of IIP [16 with idiopathic pulmonary fibrosis (IPF), 15 with idiopathic NSIP, 7 with cryptogenic organizing pneumonia (COP)] and 18 healthy volunteers.~Methods~Methods~The serum levels of autoantibodies to HSP47 in patients with idiopathic NSIP were significantly higher than in patients with IPF (P < 0.01), COP (P < 0.05), and healthy volunteers (P < 0.05). In addition, those in fibrosing NSIP were significantly higher than those of cellular and fibrosing NSIP (p < 0.05).~Results~Results~We found high levels of anti-HSP47 autoantibody titers in sera of patients with idiopathic fibrosing NSIP compared with other IIPs and healthy volunteers.~Conclusion~Conclusions [ABSTRACT FROM AUTHOR]

This retrospective cohort study analyzed data from a Japanese health insurance database to assess the effectiveness of baloxavir (n = 4822) for preventing severe events compared with oseltamivir (n = 10,523) in patients with influenza B. The primary endpoint was hospitalization incidence (Days 2-14). The secondary endpoints included intravenous antibacterial drug use, pneumonia hospitalization, heart failure hospitalization, inhalational oxygen requirement, and use of other anti-influenza drugs. The hospitalization incidence was significantly lower with baloxavir (0.15% vs. 0.37%; risk ratio: 2.48, 95% confidence interval: 1.13-5.43). Pneumonia and additional anti-influenza therapy were also less frequent with baloxavir, thus supporting its use. Trial Registration: UMIN Clinical Trials Registry Study ID: UMIN000051382., (© 2024 The Author(s). Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Cholangiocarcinoma (CCA) is a rare disease characterized by malignant cells derived from the epithelial cells of the biliary duct system. Despite extensive treatments, the prognosis for CCA remains poor, emphasizing the critical need for the development of novel treatments. Considerable attention has been directed towards innate immune effector cells, which can recognize tumor cells independently of the major histocompatibility complex, laying the foundation for the development of off-the-shelf drugs. In this study, we cultured innate immune cells obtained from the peripheral blood of healthy adults and conducted a comparative analysis of the effector functions against CCA cell lines by Vδ2 γδ T cells and NK cells. This analysis was performed using standard short- and long-term cytotoxicity assays, as well as ELISA for IFN-γ. Vδ2 γδ T cells demonstrated cytotoxicity and IFN-γ production in response to CCA cells in a TCR-dependent manner, particularly in the presence of tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino)ethylidene-1,1-bisphosphonate, a bisphosphonate prodrug. In contrast, direct killing and antibody-dependent cellular cytotoxicity were relatively slow and weak. Conversely, NK cells displayed potent, direct cytotoxicity against CCA cells. In summary, both Vδ2 γδ T cells and NK cells show promise as innate immune effector cells for adoptive transfer therapy in the context of CCA.

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., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Nocardia sputorum , a novel Nocardia species discovered in Japan in 2023, has not been reported to infect humans. Here, we report a case of pulmonary nocardiosis in a 70-year-old immunocompetent woman infected with N. sputorum . The patient presented to the hospital with a chief complaint of weight loss. She worked at a fruit sorting facility where she was exposed to dust. Chest computed tomography revealed a single cavity and diffuse nodular opacities in both lungs. Nocardia species was isolated from tracheal sputum and bronchial lavage fluid and identified as N. sputorum via 16S rRNA gene sequencing. The patient was treated with oral sulfamethoxazole and trimethoprim but developed oral mucositis on the 12th day of treatment. Consequently, minocycline was prescribed, and the patient's condition improved after a six-month course of treatment. To our knowledge, this is the first reported case of pulmonary nocardiosis caused by N. sputorum in humans. Accurate species identification and antimicrobial susceptibility tests will be necessary to prescribe appropriate treatment for Nocardia infections., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Irifune et al.)