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Papers - Namkoong, Ho

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Comprehensive Analysis of Long COVID in a Japanese Nationwide Prospective Cohort Study (preprint)

H Terai, M Ishii, R Takemura, H Namkoong, K Shimamoto, K Masaki, ...

2022

Comprehensive Analysis of Long COVID in a Japanese Nationwide Prospective Cohort Study

Hideki Terai, Makoto Ishii, Ryo Takemura, Ho Namkoong, Kyoko Shimamoto, Katsunori Masaki, Takae Tanosaki, Shotaro Chubachi, Emiko Matsuyama, Reina Hayashi, Takashi Shimada, Lisa Shigematsu, Fumimaro Ito, Masanori Kaji, Hatsuyo Takaoka, Momoko Kurihara, Kensuke Nakagawara, Saki Tomiyasu, Kotaro Sasahara, Ayaka Saito, Shiro Otake, Shuhei Azegawa, Masahiko Okada, Takahiro Fukushima, Atsuho Morita, Hiromu Tanaka, Keeya Sunata, Masato Asaoka, Miyuki Nishie, Taro Shinozaki, Toshiki Ebisudani, Yuto Akiyama, Akifumi Mitsuishi, Shingo Nakayama, Takunori Ogawa, Kaori Sakurai, Misato Kuwae, Kazuma Yagi, Keiko Ohgino, Jun Miyata, Hiroki Kabata, Shinnosuke Ikemura, Hirofumi Kamata, Hiroyuki Yasuda, Ichiro Kawada, Ryusei Kimura, Masahiro Kondo, Toshiki Iwasaki, Noriyuki Ishida, Gaku Hiruma, Naoki Miyazaki, Yoshiki Ishibashi, Sei Harada, Takanori Fujita, Daisuke Ito, Shogyoku Bun, Hajime Tabuchi, Sho Kanzaki, Eisuke Shimizu, Keitaro Fukuda, Jun Yamagami, Keigo Kobayashi, Toshiyuki Hirano, Takashi Inoue, Mizuha Hashiguchi, Junko Kagyo, Tetsuya Shiomi, Ho Lee, Kai Sugihara, Nao Omori, Koichi Sayama, Kengo Otsuka, Naoki Miyao, Toshio Odani, Takao Mochimaru, Ryosuke Satomi, Yoshitaka Oyamada, Keita Masuzawa, Takanori Asakura, Mayuko Watase, Sohei Nakayama, Yusuke Suzuki, Rie Baba, Satoshi Okamori, Daisuke Arai, Ichiro Nakachi, Naota Kuwahara, Akiko Fujiwara, Takenori Okada, Takashi Ishiguro, Taisuke Isono, Yasushi Makino, Shuko Mashimo, Tatsuya Kaido, Naoto Minematsu, Soichiro Ueda, Kazuhiro Minami, Rie Hagiwara, Tadashi Manabe, Takahiro Fukui, Yohei Funatsu, Hidefumi Koh, Takashi Yoshiyama, Hiroyuki Kokuto, Tatsuya Kusumoto, Ayano Oashi, Masayoshi Miyawaki, Fumitake Saito, Tetsuo Tani, Kota Ishioka, Saeko Takahashi, Morio Nakamura, Norihiro Harada, Hitoshi Sasano, Ai Nakamura, Yu Kusaka, Takehiko Ohba, Yasushi Nakano, Kazumi Nishio, Yukiko Nakajima, Shoji Suzuki, Shuichi Yoshida, Hiroki Tateno, Nobuhiro Kodama, Shunsuke Maeda, Satoshi Sakamoto, Masaki Okamoto, Yoji Nagasaki, Akira Umeda, Kasuya Miyagawa, Naoto Shimada, Kazuto Hagimura, Kengo Nagashima, Toshiro Sato, Yasunori Sato, Naoki Hasegawa, Toru Takebayashi, Jin Nakahara, Masaru Mimura, Kaoru Ogawa, Shigeto Shimmura, Kazuno Negishi, Kazuo Tsubota, Masayuki Amagai, Rei Goto, Yoko Ibuka, Yuko Kitagawa, Takanori Kanai, Koichi Fukunaga

SSRN Electronic Journal (Elsevier BV) 2022

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Immunohistochemical markers to diagnose primary squamous cell carcinoma of the lung: a meta-analysis of diagnostic test accuracy.

Hao Chen, Seigo Katakura, Nobuyuki Horita, Ho Namkoong, Ikuma Kato, Yu Hara, Nobuaki Kobayashi, Satoshi Fujii, Takeshi Kaneko

Therapeutic advances in medical oncology 14 17588359211065152 - 17588359211065152 2022

ISSN 1758-8340

Background: Inconsistent diagnostic test accuracies of immunohistological staining for squamous cell carcinoma (SQC) of the lung have been frequently reported. There have been few meta-analyses of the diagnostic accuracies of the immunohistochemical markers. Methods: A systematic review and meta-analysis were performed following standard guidelines for systematic reviews of diagnostic test accuracy. Immunohistochemical markers (p40, p63, CK5/6, and DSC3) were evaluated as index tests for SQC. The diagnostic odds ratio (DOR) was obtained by the DerSimonian-Laird variate model. Summary estimates of sensitivity and specificity were calculated using a bivariate model. The protocol registration ID is UMIN000041664. Results: The meta-analysis included 85 of the 1353 first-screened articles. The total number of patients was 17,893, which consisted 6151 SQC cases and 11,742 non-squamous non-small-cell lung cancer cases. The DOR was better for p40 (377, 95% confidence interval (CI) = 213-644, I 2 = 0%) than for CK5/6 (120, 95% CI = 78-184, I 2 = 2.5%), p63 (70, 95% CI = 55-88, I 2 = 9.1%), and DSC3 (94, 95% CI = 35-250, I 2 = 3.7%). Summary estimates of sensitivity and specificity were followings: p40 sensitivity 0.92 (95% CI = 0.89-0.95), specificity 0.94 (95% CI = 0.93-0.96); p63 sensitivity 0.92 (95% CI = 0.90-0.94), specificity 0.83 (95% CI = 0.80-0.86); CK5/6 sensitivity 0.90 (95% CI = 0.87-0.93), specificity 0.91 (95% CI = 0.89-0.93); DSC3 sensitivity 0.81 (95% CI = 0.73-0.88), and specificity 0.95 (95% CI = 0.85-0.98). Conclusion: P40 had the best DOR to diagnose SQC in non-small-cell lung carcinoma. Despite its lower sensitivity, DSC3 had the best specificity among the four markers and might be useful to rule-in the diagnosis of SQC.

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POS0257 COMPARISON OF SARS-CoV-2 VACCINE RESPONSE IN PATIENTS WITH INFLAMMATORY RHEUMATIC DISEASE; mRNA-1273 VACCINE INDUCES HIGHER HUMORAL IMMUNOGENICITY THAN BNT162b2

Y Kondo, M Takeshita, Y Uwamino, H Namkoong, S Saito, J Kikuchi, ...

Annals of the Rheumatic Diseases 81 (Suppl 1), 370-370 2022

Mycoplasma pneumoniae beyond the COVID-19 pandemic: where is it?

PMM Sauteur, VJ Chalker, C Berger, R Nir-Paz, ML Beeton, S Pereyre, ...

The Lancet Microbe 3 (12), e897 2022

Memory B cells and memory T cells induced by SARS-CoV-2 booster vaccination or infection show different dynamics and efficacy to the Omicron variant.

S Mise-Omata, M Ikeda, M Takeshita, Y Uwamino, M Wakui, T Arai, ...

bioRxiv, 2022.07. 31.500554 2022

Incidence of hepatotoxicity associated with addition of immune checkpoint blockade to systemic solid tumor therapy: a meta-analysis of phase 3 randomized controlled trials

Y Fujiwara, N Horita, M Harrington, H Namkoong, H Miyashita, MD Galsky

Cancer Immunology, Immunotherapy 71 (12), 2837-2848 2022

Incidence and Distinct Features of Immune Checkpoint Inhibitor-Related Myositis From Idiopathic

N Hamada, A Maeda, K Takase-Minegishi, Y Kirino, Y Sugiyama, ...

Autoimmune Myositis: From Immunological to Rheumatological Aspects 2022

Clinical Characteristics of Patients with Coronavirus Disease (COVID-19): Preliminary Baseline Report of Japan COVID-19 Task Force, a Nationwide Consortium to Investigate Host Genetics of COVID-19.

Hiromu Tanaka, Ho Lee, Atsuho Morita, Ho Namkoong, Shotaro Chubachi, Hiroki Kabata, Hirofumi Kamata, Makoto Ishii, Naoki Hasegawa, Norihiro Harada, Tetsuya Ueda, Soichiro Ueda, Takashi Ishiguro, Ken Arimura, Fukuki Saito, Takashi Yoshiyama, Yasushi Nakano, Yoshikazu Mutoh, Yusuke Suzuki, Koji Murakami, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Katsushi Tokunaga, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 113 74 - 81 2021.12

ISSN 1201-9712

BACKGROUND AND DESIGN: The coronavirus disease (COVID-19) pandemic is having a devastating effect worldwide. Host genome differences between populations may influence the severity of COVID-19. The Japan COVID-19 Task Force is conducting host genome analysis of hospitalized patients with COVID-19 from more than 70 institutions nationwide in Japan. This report describes the clinical characteristics of patients enrolled to date. RESULTS: The median (interquartile range) age of the 1674 patients included in the analysis was 59 (45-71) years, and more than half of the patients (66.2%) were male. Less than half of the patients (41.2%) had severe disease. The case fatality rate was 3.2%. CONCLUSIONS: Since this is a hospital-based study, the number of severe cases was relatively high, but the case fatality rate was relatively low, when compared to that of other countries. In the future, we will continue to enroll patients and conduct genome analyses of patients with COVID-19.

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Beneficial Effects of Apremilast on Genital Ulcers, Skin Lesions, and Arthritis in Patients With Behçet's Disease: A Systematic Review and Meta-Analysis.

Yuki Iizuka, Kaoru Takase-Minegishi, Lisa Hirahara, Yohei Kirino, Yutaro Soejima, Ho Namkoong, Nobuyuki Horita, Ryusuke Yoshimi, Masaki Takeuchi, Mitsuhiro Takeno, Nobuhisa Mizuki, Hideaki Nakajima

Modern rheumatology 32 ( 6 ) 1153 - 1162 2021.11

ISSN 1439-7595

OBJECTIVE: This study aimed to determine the clinical efficacy of apremilast for oral ulcers, extra-oral manifestations, and overall disease activity in patients with Behçet's disease (BD). METHODS: A systematic literature search was performed in PubMed, EMBASE, Cochrane Library, and Web of Science Core Collection. Studies assessing the treatment effects of apremilast in BD were included. The odds ratios (ORs) of being symptom free for individual manifestations and mean difference (MD) of Behçet's Disease Current Activity Form (BDCAF) scores were calculated with 95% confidence intervals (CIs) at 12 and 24 weeks using a random-model meta-analysis. RESULTS: Of 259 screened articles, eight were included. After 12 weeks of apremilast treatment the OR of symptom-free was as followings: oral ulcers, 45.76 (95% CI, 13.23-158.31); genital ulcers, 4.56 (95% CI, 2.47-8.44); erythema nodosum, 3.59 (95% CI, 1.11-11.61); pseudofolliculitis, 2.81 (95% CI, 1.29-6.15); and arthritis, 3.55 (95% CI, 1.71-7.40). Furthermore, BDCAF scores at 12 weeks were significantly reduced (MD=-1.38; -1.78 to -0.99). However, the proportion of oral-ulcer free patients increased at 24 weeks (OR=14.88; 4.81 to 46.07). CONCLUSION: The currently accumulated data indicates an improvement in mucocutaneous and articular symptoms by short-term apremilast treatment in patients with BD.

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Comprehensive and long-term surveys of COVID-19 sequelae in Japan, an ambidirectional multicentre cohort study: study protocol.

Kensuke Nakagawara, Ho Namkoong, Hideki Terai, Katsunori Masaki, Takae Tanosaki, Kyoko Shimamoto, Ho Lee, Hiromu Tanaka, Satoshi Okamori, Hiroki Kabata, Shotaro Chubachi, Shinnosuke Ikemura, Hirofumi Kamata, Hiroyuki Yasuda, Ichiro Kawada, Makoto Ishii, Yoshiki Ishibashi, Sei Harada, Takanori Fujita, Daisuke Ito, Shogyoku Bun, Hajime Tabuchi, Sho Kanzaki, Eisuke Shimizu, Keitaro Fukuda, Jun Yamagami, Keigo Kobayashi, Toshiyuki Hirano, Takashi Inoue, Junko Kagyo, Tetsuya Shiomi, Keiko Ohgino, Koichi Sayama, Kengo Otsuka, Naoki Miyao, Toshio Odani, Yoshitaka Oyamada, Keita Masuzawa, Sohei Nakayama, Yusuke Suzuki, Rie Baba, Ichiro Nakachi, Naota Kuwahara, Takashi Ishiguro, Shuko Mashimo, Naoto Minematsu, Soichiro Ueda, Tadashi Manabe, Yohei Funatsu, Hidefumi Koh, Takashi Yoshiyama, Fumitake Saito, Kota Ishioka, Saeko Takahashi, Morio Nakamura, Ai Goto, Norihiro Harada, Yu Kusaka, Yasushi Nakano, Kazumi Nishio, Hiroki Tateno, Ryuya Edahiro, Yoshito Takeda, Atsushi Kumanogoh, Nobuhiro Kodama, Masaki Okamoto, Akira Umeda, Kazuto Hagimura, Toshiro Sato, Naoki Miyazaki, Ryo Takemura, Yasunori Sato, Toru Takebayashi, Jin Nakahara, Masaru Mimura, Kaoru Ogawa, Shigeto Shimmura, Kazuno Negishi, Kazuo Tsubota, Masayuki Amagai, Rei Goto, Yoko Ibuka, Naoki Hasegawa, Yuko Kitagawa, Takanori Kanai, Koichi Fukunaga

BMJ open respiratory research 8 ( 1 ) 2021.11

INTRODUCTION: The rapid spread of COVID-19 posed a global burden. Substantial number of people died of the disease in the acute phase of infection. In addition, a significant proportion of patients have been reported to suffer from post-acute phase symptoms, sequelae of COVID-19, which may negatively influence the quality of daily living and/or socioeconomic circumstances of the patients. However, no previous study has comprehensively and objectively assessed the quality of life of patients by using existing international scales. Further, evidence of socioeconomic consequences among patients with COVID-19 is scarce. To address the multidimensional issues from sequelae of COVID-19, evidence from comprehensive surveys beyond clinical perspectives is critical that investigates health, and social determinants of disease progression as well as socioeconomic consequences at a large scale. METHODS AND ANALYSIS: In this study, we plan to conduct a nationwide and comprehensive survey for the sequelae of COVID-19 in a total of 1000 patients diagnosed at 27 hospitals throughout Japan. This study will evaluate not only the health-related status of patients from clinical perspectives but also the Health-related Quality of Life (HRQoL) scores, socioeconomic status and consequences to discuss the sequelae of the disease and the related risk factors. The primary endpoint is the frequency of long-term complications of COVID-19 infection. The secondary endpoints are risk factors for progression to sequelae of COVID-19 infection. The study will provide robust and important evidence as a resource to tackle the issues from the sequelae of COVID-19 from the multi-dimensional perspectives. ETHICS AND DISSEMINATION: This trial was approved by the Keio University School of Medicine Ethics Committee (20200243, UMIN000042299). The results of this study will be reported at a society meeting or published in a peer-reviewed journal.

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Cardiac tamponade due to primary malignant pericardial mesothelioma diagnosed with surgical pericardial resection.

Naoki Kawakami, Miki Kawai, Ho Namkoong, Daisuke Arai, Soichiro Ueda, Kenichi Hamada, Ichiro Kawada, Naoki Hasegawa, Shuji Mikami, Hisao Asamura, Koichi Fukunaga

Journal of cardiology cases 24 ( 4 ) 149 - 152 2021.10

Primary malignant pericardial mesothelioma is an extremely rare disease. Malignant disease of the pericardium is an infrequent cause of cardiac tamponade. Hence, cardiac tamponade in the context of primary malignant mesothelioma of the pericardium is an uncommon clinical scenario. A 67-year-old male patient, an ex-smoker, complaining of progressive lethargy was referred to a hospital for investigation of persistent pericardial effusion. The pericardial fluid cytology was categorized as class Ⅲ. Thereafter, he was referred to our hospital for further evaluation. Fluorodeoxyglucose (FDG) positron emission tomography (PET) revealed FDG accumulation in the pericardium and mediastinal lymph node. Surgical biopsy of the pericardium was performed through a subxiphoid approach for a definitive diagnosis. Histopathological examination revealed diffuse infiltration of the pericardium by a malignant tumor consisting of epithelioid cells with large round nuclei and prominent nucleoli, arranged in a tubular papillary pattern. Finally, the patient was diagnosed with primary malignant pericardial mesothelioma of epithelioid type. The patient died 6 weeks after admission. This diagnosis must be considered in patients having unexplained massive pericardial effusion. Furthermore, we should consider prompt cytological analysis and FDG PET to arrive rapidly at a definitive diagnosis to administer combination chemotherapy that may provide clinical benefit. <Learning objective: Primary malignant pericardial mesothelioma is a rare disease. Malignant disease of the pericardium is an infrequent cause of cardiac tamponade. Hence, cardiac tamponade in the context of primary malignant mesothelioma of the pericardium is an uncommon clinical scenario. However, this diagnosis must be considered in patients having unexplained massive pericardial effusion. Furthermore, we should consider prompt cytological analysis and fluorodeoxyglucose positron emission tomography to arrive rapidly at a definitive diagnosis to administer combination chemotherapy that may provide clinical benefit.>.

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ADAM10 Partially Protects Mice against Influenza Pneumonia by Suppressing Specific Myeloid Cell Population.

Satoshi Okamori, Makoto Ishii, Takanori Asakura, Shoji Suzuki, Ho Namkoong, Shizuko Kagawa, Ahmed E Hegab, Kazuma Yagi, Hirofumi Kamata, Tatsuya Kusumoto, Takunori Ogawa, Hayato Takahashi, Masaki Yoda, Keisuke Horiuchi, Naoki Hasegawa, Koichi Fukunaga

American journal of physiology. Lung cellular and molecular physiology 321 ( 5 ) L872-L884 - L884 2021.09

ISSN 1040-0605

The influenza virus infection poses a serious health threat worldwide. Myeloid cells play pivotal roles in regulating innate and adaptive immune defense. A disintegrin and metalloproteinase (ADAM) family of proteins contribute to various immune responses; however, the role of ADAM10 in influenza virus infection remains largely unknown. Herein, we investigated its role, focusing on myeloid cells, during influenza virus infection in mice. Adam10flox/flox/Lyz2-Cre (Adam10ΔLyz2) and control Adam10flox/flox mice were intranasally infected with 200 plaque-forming units of influenza virus A/H1N1/PR8/34. Adam10ΔLyz2 mice exhibited a significantly higher mortality rate, stronger lung inflammation, and a higher virus titer in the lungs than control mice. Macrophages and inflammatory cytokines such as TNF-α, IL-1b, and CCL2 were increased in bronchoalveolar lavage fluid from Adam10ΔLyz2 mice following infection. CD11b+Ly6G-F4/80+ myeloid cells, which had an inflammatory monocytes/macrophages-like phenotype, were significantly increased in the lungs of Adam10ΔLyz2 mice. Adoptive transfer experiments suggested that these cells likely contributed to the poorer prognosis in Adam10ΔLyz2 mice. Seven days after infection, CD11b+Ly6G-F4/80+ lung cells exhibited significantly higher arginase-1 expression levels in Adam10ΔLyz2 mice than in control mice, while an arginase-1 inhibitor improved the prognosis of Adam10ΔLyz2 mice. Enhanced granulocyte-macrophage colony-stimulating factor (GM-CSF)/GM-CSF receptor signaling likely contributed to this process. Collectively, these results indicate that myeloid ADAM10 protects against influenza virus pneumonia and may be a promising therapeutic target.

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Anal tuberculosis presenting as refractory perianal abscess.

Kotaro Sasahara, Keiichiro Kitahama, Satoshi Aiko, Ho Namkoong

Clinical case reports 9 ( 9 ) e04177 2021.09

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Rheumatoid arthritis with nontuberculous mycobacterial pulmonary disease: a retrospective, single-centre cohort study.

Hiroshi Takei, Naoshi Nishina, H O Namkoong, Katsuya Suzuki, Yoshifumi Uwamino, Naoki Hasegawa, Tsutomu Takeuchi

Modern rheumatology 32 ( 3 ) 534 - 540 2021.08

ISSN 1439-7595

OBJECTIVES: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a rare but important comorbidity of rheumatoid arthritis (RA). Our objective was to investigate the association between NTM-PD and RA, especially regarding the immunosuppressive treatment of RA such as biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: We conducted a retrospective, single-centre cohort study. All RA patients regularly followed up at our rheumatology division in December 2012 were included in the study, and followed for 5 years. RESULTS: At baseline, 26 of 1639 RA patients had NTM-PD. During the observation period, 14 were newly diagnosed with NTM-PD. For new diagnosis of NTM-PD, bDMARD use at baseline was not a significant risk factor. Among the 40 patients with NTM-PD, 16 were treated with a total of 27 bDMARDs after NTM-PD diagnosis. They did not present with a greater exacerbation of NTM-PD than those not treated with bDMARDs (25 vs. 17%, p = .52). A total of 55 patients died, but nobody died of NTM-PD. NTM-PD was not associated with worse mortality in multivariate analysis (hazard ratio, 2.0; 95% CI, 0.6-6.4; p = .26). CONCLUSIONS: Biological DMARD was not associated with worse prognosis of NTM-PD. Careful use of bDMARDs could be tolerated in RA patients with NTM-PD.

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Genome-wide association study in patients with pulmonary Mycobacterium avium complex disease

Namkoong Ho, Omae Yosuke, Asakura Takanori, Ishii Makoto, Suzuki Shoji, Morimoto Kozo, Kawai Yosuke, Emoto Katsura, Oler Andrew J., Szymanski Eva P., Yoshida Mitsunori, Matsuda Shuichi, Yagi Kazuma, Hase Isano, Nishimura Tomoyasu, Sasaki Yuka, Asami Takahiro, Shiomi Tetsuya, Matsubara Hiroaki, Shimada Hisato, Hamamoto Junko, Jhun Byung Woo, Kim Su-Young, Huh Hee Jae, Won Hong-Hee, Ato Manabu, Kosaki Kenjiro, Betsuyaku Tomoko, Fukunaga Koichi, Kurashima Atsuyuki, Tettelin Herve, Yanai Hideki, Mahasirimongkol Surakameth, Olivier Kenneth N., Hoshino Yoshihiko, Koh Won-Jung, Holland Steven M., Tokunaga Katsushi, Hasegawa Naoki

EUROPEAN RESPIRATORY JOURNAL 58 ( 2 ) 2021.08

ISSN 0903-1936

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Genome-wide association study in patients with pulmonary Mycobacterium avium complex disease.

Namkoong H, Omae Y, Asakura T, Ishii M, Suzuki S, Morimoto K, Kawai Y, Emoto K, Oler AJ, Szymanski EP, Yoshida M, Matsuda S, Yagi K, Hase I, Nishimura T, Sasaki Y, Asami T, Shiomi T, Matsubara H, Shimada H, Hamamoto J, Jhun BW, Kim SY, Huh HJ, Won HH, Ato M, Kosaki K, Betsuyaku T, Fukunaga K, Kurashima A, Tettelin H, Yanai H, Mahasirimongkol S, Olivier KN, Hoshino Y, Koh WJ, Holland SM, Tokunaga K, Hasegawa N, Nontuberculous Mycobacteriosis and Bronchiectasis – Japan Research Consortium (NTM-JRC)

The European respiratory journal 58 ( 2 ) 2021.08

ISSN 0903-1936

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The best regimens for chemo-naïve incurable non-squamous non-small cell lung cancer with a programmed death-ligand 1, tumor proportion score 1-49%: a network meta-analysis.

Nobuhiko Fukuda, Nobuyuki Horita, Seigo Katakura, Ho Namkoong, Ayami Kaneko, Kouhei Somekawa, Youichi Tagami, Keisuke Watanabe, Yu Hara, Nobuaki Kobayashi, Takeshi Kaneko

Translational lung cancer research 10 ( 8 ) 3550 - 3566 2021.08

ISSN 2218-6751

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. There is a rank order of the efficacy and safety of treatment options, including immune checkpoint inhibitors (ICIs), bevacizumab (Bev), and cytotoxic drugs. When patients have low programmed death-ligand 1 (PD-L1) expression, there are multiple options for treatment. In this study, we focused on ICI regimens in patients with non-squamous NSCLC with low PD-L1 expression and no driver alterations and assessed the efficacy of the regimens using network meta-analysis. Methods: Randomized trials for incurable chemo-naïve non-squamous NSCLC were collected through electronic searches. The data were independently extracted and cross-checked by two investigators. The primary outcome of this analysis was overall survival (OS). A frequentist weighted least-squares approach random-model network meta-analysis was applied. Results: Sixty-eight eligible studies and 22,619 patients were identified. Using a platinum + third-generation cytotoxic agent regimen (platinum regimen) as a reference, the platinum regimen + pembrolizumab (Pemb) [hazard ratio (HR) =0.55, 95% confidence interval (CI): 0.34-0.89, P=0.015] showed the best OS, followed by the platinum regimen + nivolumab (Niv) + ipilimumab (Ipi) (HR =0.61, 95% CI: 0.44-0.84, P=0.003) with no heterogeneity (I2=0%, P=0.348). Conclusions: The addition of Pemb or Niv/Ipi to platinum-based chemotherapy seems to be a good therapeutic option for non-squamous NSCLC with a PD-L1 tumor proportion score (TPS) of 1-49%.

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Diagnostic accuracy of Aspergillus-specific antibodies for chronic pulmonary aspergillosis: A systematic review and meta-analysis.

Keisuke Anan, Yuki Kataoka, Shinji Okabayashi, Ryohei Yamamoto, Ho Namkoong, Yosuke Yamamoto

Mycoses 64 ( 7 ) 701 - 715 2021.07

ISSN 0933-7407

We performed this study to provide the latest evidence of the diagnostic accuracy of all Aspergillus antibodies for chronic pulmonary aspergillosis (CPA). In this meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and other databases, until 19 March 2020, for studies that examined the diagnostic accuracy of each Aspergillus-specific antibody for CPA and assessed the risk of bias using the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool. We integrated the results using a hierarchical summary receiver operating characteristic (HSROC) model and calculated the point estimates of specificity with sensitivity fixed at 0.90 using the HSROC curve. We identified 32 published and one unpublished studies, including 75 studies on five antibody test types: 18 of precipitin test (2810 participants), 46 of IgG (8197), three of IgA (283), six of IgM (733) and two of combined IgG and IgM (IgG + IgM) (920). The results of specificity with sensitivity fixed at 0.90 were as follows: precipitin test, 0.93 (95% credible intervals: 0.86, 1.00); IgG, 0.90 (0.86, 0.95); IgA, 0.74 (0.00, 1.00); IgM, 0.50 (0.37, 0.53); IgG + IgM, 0.47 (0.00, 1.00). However, the precipitin test showed imprecision and instability in the sensitivity analysis. Most studies had a high risk of bias due to the case-control design. Although there is lack of applicability for malignancy or immunosuppressive patients, our study suggests a preference for IgG over other antibody tests in CPA screening. Particularly, IgG should be used as an adjunct when ruling out CPA.

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Longitudinal validity and prognostic significance of the St George's Respiratory Questionnaire in Mycobacterium avium complex pulmonary disease.

Takunori Ogawa, Takanori Asakura, Shoji Suzuki, Satoshi Okamori, Tatsuya Kusumoto, Yasunori Sato, Ho Namkoong, Hirofumi Kamata, Makoto Ishii, Koichi Fukunaga, Naoki Hasegawa

Respiratory medicine 185 106515 - 106515 2021.06

ISSN 0954-6111

BACKGROUND: Although previous cross-sectional studies showed the feasibility and clinical association of the St. George's Respiratory Questionnaire (SGRQ) in Mycobacterium avium complex pulmonary disease (MAC-PD), its longitudinal validity is poorly understood. We aimed to determine the longitudinal validity and prognostic significance of SGRQ. METHODS: In this prospective observational study conducted between May 2012 and August 2018, we evaluated 269 enrolled patients with MAC-PD and examined associations between baseline SGRQ total scores and mortality or clinical variables (anchors), including serum C-reactive protein levels and pulmonary function test results. RESULTS: Age- and sex-matched SGRQ scores indicated significantly greater impairment in patients with MAC-PD than in the general population (P < 0.001). On multivariable Cox proportional hazards regression analysis, the SGRQ total score ≥25 was an independent risk factor for mortality (adjusted hazard ratio, 5.90; 95% confidence interval, 1.65-37.7) as well as age, body mass index, and forced vital capacity (FVC). Mixed-effect model results showed a significant association between SGRQ symptom/total scores and forced expiratory volume in 1 s (FEV1), FVC, and diffusing carbon monoxide capacity. Older age, a positive smear, non-nodular/bronchiectatic form, and cavity regions were associated with SGRQ total score deterioration. Patients with a greater decline from baseline FEV1 (% predicted) exhibited significantly worse impairment in the SGRQ total score (mean ± SE, 4.69 ± 10.9 points, P = 0.001). CONCLUSIONS: SGRQ showed longitudinal validity in assessing disease severity and was sensitive to changes in patients with MAC-PD, especially changes in %FEV1. The SGRQ total score may be an important prognostic factor.

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