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Masanori Kaji,1 Ho Namkoong,2 Genta Nagao,1 Shuhei Azekawa,1 Kensuke Nakagawara,1 Hiromu Tanaka,1 Atsuho Morita,1 Takanori Asakura,1,3,4 Hirofumi Kamata,1 Yoshifumi Uwamino,2,5 Mitsunori Yoshida,6 Koichi Fukunaga,1 Naoki Hasegawa2 1Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan; 3Department of Clinical Medicine (Laboratory of Bioregulatory Medicine), Kitasato University School of Pharmacy, Tokyo, Japan; 4Department of Respiratory Medicine, Kitasato University, Kitasato Institute Hospital, Tokyo, Japan; 5Department of Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan; 6Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, JapanCorrespondence: Ho Namkoong, Department of Infectious Diseases, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan, Tel + 3-3353-1211 61164, Fax + 3-3353-5958, Email hounamugun@gmail.comBackground: Mycobacterium abscessus (M. abscessus) is a rapidly growing bacterium (RGM) that causes refractory pulmonary and extrapulmonary infections. However, studies investigating pharyngeal and laryngeal M. abscessus infections are limited.Case Presentation: A 41-year-old immunocompetent woman complaining of bloody sputum was referred to our hospital. Although her sputum culture tested positive for M. abscessus subsp. abscessus, radiological findings were not indicative of pulmonary infection or sinusitis. Further diagnostic workup, including laryngeal endoscopy and positron emission tomography/computed tomography (PET/CT), confirmed the presence of nasopharyngeal M. abscessus infection. The patient was initially treated with intravenous amikacin, imipenem/cilastatin, azithromycin, and clofazimine for 28 days, after which the patient was provided with amikacin, azithromycin, clofazimine, and sitafloxacin for four months. After the completion of antibiotic therapy, the patient showed negative results on sputum smear and culture and normal findings on PET/CT and laryngeal endoscopy. Whole-genome sequencing of this strain revealed that it belonged to the ABS-GL4 cluster, which has a functional erythromycin ribosomal methylase gene, although it is not a major lineage in non-cystic fibrosis (CF) patients in Japan and Taiwan and in CF patients in European countries. We conducted a literature review and identified seven patients who developed pharyngeal/laryngeal non-tuberculous mycobacterium (NTM) infection. Four of the eight patients had a history of immunosuppressant use, including steroids. Seven of the eight patients responded well to their treatment regimens.Conclusion: Patients whose sputum culture tests are positive for NTM and who meet the diagnostic criteria for NTM infection but do not have intrapulmonary lesions should be evaluated for otorhinolaryngological infections. Our case series revealed that immunosuppressant use is a risk factor for pharyngeal/laryngeal NTM infection and that patients with pharyngeal/laryngeal NTM infections respond relatively well to antibiotic therapy.Keywords: pharyngeal NTM, laryngeal NTM, whole-genome sequencing

Atsuho Morita,1 Ho Namkoong,2 Kazuma Yagi,1 Takanori Asakura,1 Makoto Hosoya,3 Hiromu Tanaka,1 Ho Lee,1 Takunori Ogawa,1 Tatsuya Kusumoto,1 Shuhei Azekawa,1 Kensuke Nakagawara,1 Hirofumi Kamata,1 Makoto Ishii,1 Koichi Fukunaga,1 Hiroyuki Ozawa,3 Naoki Hasegawa2 1Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan; 3Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, Tokyo, JapanCorrespondence: Ho Namkoong, Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan, Tel +81 03 3353 1211, Fax +81 03 5843 6167, Email hounamugun@gmail.comPurpose: Amikacin liposome inhalation suspension (ALIS), which efficiently allows amikacin to reach the pulmonary periphery for effect while minimising systemic adverse effects, was recently approved for treating Mycobacterium avium complex (MAC) infections. The international Phase 3 open-label clinical trials showed promising results, contributing to sputum culture conversion, but few studies have examined the efficacy and adverse effects of ALIS using real-world data. We identified the clinical outcome and adverse effects of ALIS in the early phase of treatment, for more effective and safe use in clinical practice.Patients and Methods: The study population consisted of patients with MAC lung disease (MAC-LD), introduced to ALIS therapy after July 2021 at Keio University Hospital due to poor response to multidrug therapy. The sputum smear/culture results, symptoms, adverse effects, and the serum amikacin concentrations of the early phase of ALIS inhalation therapy were examined.Results: A total of 11 patients (9 women; median age 64.6 years) were included in this study. The median disease duration of MAC-LD was 13.7 years, and all patients exhibited a positive culture at the beginning of ALIS inhalation. Three of the six patients (50.0%) who were initially sputum-smear-positive were confirmed to have become sputum-smear-negative within one month, including one culture conversion. ALIS inhalation therapy caused some adverse effects in nine patients (81.8%); however, no serious systemic adverse effects were observed. The most common adverse effect was hoarseness (72.7%), which mostly occurred around 1 week after initiation. The medians of peak serum amikacin concentrations were 1.4 and 2.3 μg/mL for the first and third inhalations, respectively. Trough serum concentrations just before the third inhalation were < 1.2 μg/mL in all patients.Conclusion: ALIS therapy might be a treatment option for patients with refractory MAC infection with long disease duration and a poor response to guideline-based therapy.Keywords: Mycobacterium avium complex, MAC, nontuberculous mycobacteria, NTM, amikacin liposome inhalation suspension, ALIS

Hiromu Tanaka,1 Takanori Asakura,1 Jun Kikuchi,2 Makoto Ishii,1 Ho Namkoong,3 Yuko Kaneko,2 Koichi Fukunaga,1 Naoki Hasegawa3 1Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan; 2Division of Rheumatology, Department of Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan; 3Department of Infectious Diseases, Keio University School of Medicine, Shinjuku-ku, Tokyo, JapanCorrespondence: Takanori AsakuraDivision of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, JapanTel +81-3-3353-1211Fax +81-3-3353-2502Email takanori.asakura@keio.jpBackground: Nontuberculous mycobacterial pulmonary disease (NTM-PD) often develops in patients with rheumatoid arthritis (RA), especially during immunosuppressive treatment, including biological disease-modifying antirheumatic drugs. NTM-PD is associated with airway lesions such as bronchiectasis, which is frequently seen in RA patients. Distinguishing which diseases cause the pulmonary lesion is difficult. However, there are limited reports of the development of RA during the follow-up of NTM-PD and how biological agents should be administered in these conditions, especially with cavitary lesions.Case Presentation: A 62-year-old woman with hemosputum was referred to our hospital, where she was diagnosed with Mycobacterium avium pulmonary disease. She began treatment with several antibiotics, including clarithromycin, ethambutol, rifampicin, and amikacin. In the course of treatment, M. avium became macrolide-resistant. Five years after beginning antibiotic treatment, she felt arthralgia in the fingers and wrists and had a high titer of rheumatoid factor and anticitrullinated peptide antibody, with which we diagnosed RA. Methotrexate, prednisolone, and iguratimod were subsequently administered, but the activity of RA gradually worsened. Meanwhile, M. avium changed to a macrolide-susceptible strain, her sputum smear results remained almost negative, and the NTM-PD disease was well controlled with antimicrobial therapy, despite her having cavitary lesions. Therefore, we started using CTLA4-Ig (abatacept). RA symptoms were substantially ameliorated. The pulmonary lesions and NTM-PD worsened mildly, but her pulmonary symptoms were stable.Conclusion: Physicians should be mindful of the etiologies of bronchiectasis, including RA, even in patients with a long-term history of treatment for bronchiectasis and NTM-PD. When NTM-PD is well controlled, even with remaining cavitary lesions, abatacept may be an option for patients with RA based on a comprehensive assessment of disease progression using NTM sputum smear/culture, computed tomography findings, and treatment response.Keywords: rheumatoid arthritis, nontuberculous mycobacterial infection, cavitary lesion, biological agent, bronchiectasis

Tetsuyuki Suetsugu,1,2 Aki Kato,1 Munenori Yoshida,1 Tsutomu Yasukawa,1 Akiko Nishiwaki,1,3 Norio Hasegawa,1 Hideaki Usui,1 Yuichiro Ogura1 1Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, 2Department of Ophthalmology, General Kamiiida Daiichi Hospital, 3Nishiwaki Eye Clinic, Nagoya, Aichi, Japan Purpose: We aimed to evaluate the prevalence of abnormal peripheral fundus autofluorescence (FAF) in wet age-related macular degeneration (AMD) using wide-field imaging instrument. Patients and methods: A retrospective, case-controlled study involving 66 eyes of 46 Japanese wet AMD patients and 32 eyes of 20 control patients was performed. Wide-field FAF images were obtained for typical AMD (37 eyes/28 patients), polypoidal choroidal vasculopathy (PCV) (22 eyes/20 patients), and retinal angiomatous proliferation (RAP) (seven eyes/four patients). Two masked ophthalmologists independently graded the images for mottled, granular, and nummular patterns. Main outcome measures were abnormal peripheral FAF frequencies and relative risks by disease subgroups and treatments. Results: Abnormal peripheral FAF patterns were found in 51.5% of wet AMD eyes compared with 18.8% of control eyes (P