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Papers - Namkoong, Ho

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特集 1ページでわかる内科疾患の診療ノート-"あたりまえ" のなかにある大事な視点第5章:感染症肺非結核性抗酸菌症

南宮湖

内科 (南江堂) 129 ( 4 ) 749 - 753 2022.04

ISSN 00221961

Cardiac involvement in coronavirus disease 2019 assessed by cardiac magnetic resonance imaging: a meta-analysis.

Shingo Kato, Mai Azuma, Kazuki Fukui, Sho Kodama, Naoki Nakayama, Hideya Kitamura, Eri Hagiwara, Takashi Ogura, Nobuyuki Horita, Ho Namkoong, Kazuo Kimura, Kouichi Tamura, Daisuke Utsunomiya

Heart and vessels 37 ( 9 ) 1570 - 1582 2022.03

ISSN 0910-8327

In this systematic review and meta-analysis, we sought to evaluate the prevalence of cardiac involvement in patients with COVID-19 using cardiac magnetic resonance imaging. A literature review was performed to investigate the left ventricular (LV) and right ventricular (RV) ejection fraction (EF), the prevalence of LV late gadolinium enhancement (LGE), pericardial enhancement, abnormality on T1 mapping, and T2 mapping/T2-weighted imaging (T2WI), and myocarditis (defined by modified Lake Louis criteria). Pooled mean differences (MD) between COVID-19 patients and controls for LVEF and RVEF were estimated using random-effects models. We included data from 10.462 patients with COVID-19, comprising 1.010 non-athletes and 9.452 athletes from 29 eligible studies. The meta-analysis showed a significant difference between COVID-19 patients and controls in terms of LVEF [MD = - 2.84, 95% confidence interval (CI) - 5.11 to - 0.56, p < 0.001] and RVEF (MD = - 2.69%, 95% CI - 4.41 to - 1.27, p < 0.001). However, in athletes, no significant difference was identified in LVEF (MD = - 0.74%, 95% CI - 2.41 to - 0.93, p = 0.39) or RVEF (MD = - 1.88%, 95% CI - 5.21 to 1.46, p = 0.27). In non-athletes, the prevalence of LV LGE abnormalities, pericardial enhancement, T1 mapping, T2 mapping/T2WI, myocarditis were 27.5% (95%CI 17.4-37.6%), 11.9% (95%CI 4.1-19.6%), 39.5% (95%CI 16.2-62.8%), 38.1% (95%CI 19.0-57.1%) and 17.6% (95%CI 6.3-28.9%), respectively. In athletes, these values were 10.8% (95%CI 2.3-19.4%), 35.4% (95%CI - 3.2 to 73.9%), 5.7% (95%CI - 2.9 to 14.2%), 1.9% (95%CI 1.1-2.7%), 0.9% (0.3-1.6%), respectively. Both LVEF and RVEF were significantly impaired in COVID-19 patients compared to controls, but not in athletes. In addition, the prevalence of myocardial involvement is not negligible in patients with COVID-19.

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Benefits and risks of Hematopoietic Stem Cell Transplantation for Systemic Sclerosis: A Systematic Review and Meta-Analysis.

Kana Higashitani, Kaoru Takase-Minegishi, Ryusuke Yoshimi, Yohei Kirino, Naoki Hamada, Hideto Nagai, Maki Hagihara, Kenji Matsumoto, Ho Namkoong, Nobuyuki Horita, Hideaki Nakajima

Modern rheumatology 33 ( 2 ) 330 - 337 2022.03

ISSN 1439-7595

OBJECTIVES: We aimed to evaluate the efficacy and safety of hematopoietic stem cell transplantation (HSCT) in patients with systemic sclerosis (SSc). METHODS: A systematic literature review and meta-analysis were carried out. We compared survival outcomes using the Kaplan-Meier method with patient-level data between HSCT and intravenous pulse cyclophosphamide (IVCY). Additionally, the incidence rate of treatment-related deaths with HSCT was pooled using a random-effect model. RESULTS: Of the 2,091 articles screened, 22 were included: 3 randomized controlled trials and 19 observational studies. HSCT studies showed significant improvement in the skin thickness score and lung function. Despite treatment-related deaths being higher in HSCT than in IVCY, the Kaplan-Meier analysis showed a high survival rate 2 years post-transplant (log-rank, P=0.004). The pooled frequency of transplant-related death from 700 SSc patients was 6.30% (95% confidence interval 4.21-8.38). However, the estimated frequency of treatment-related deaths has been reducing over the last decade. CONCLUSION: HSCT is an effective treatment for SSc, but the optimal indications must be carefully determined by balancing the risks.

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Laryngitis after inhalation of liposomal amikacin.

Atsuho Morita, Ho Namkoong, Makoto Hosoya, Naoki Hasegawa

Clinical case reports 10 ( 2 ) e05350 2022.02

ISSN 2050-0904

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特集 COVID-19と腎臓病【総論】予後予測因子

田中拓, 南宮湖

腎と透析 (東京医学社) 92 ( 1 ) 35 - 40 2022.01

ISSN 03852156

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

Nobuhiko Fukuda, Nobuyuki Horita, Ho Namkoong, Ayami Kaneko, Kohei Somekawa, Yoichi Tagami, Keisuke Watanabe, Yu Hara, Nobuaki Kobayashi, Takeshi Kaneko

Thoracic cancer 13 ( 1 ) 84 - 94 2022.01

ISSN 1759-7706

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. It is advisable to select the appropriate treatment based on characteristics of the cancer such as pathology, mutations, and programmed death-ligand 1 (PD-L1) levels. In this study, by remarking squamous NSCLC with low PD-L1 expression without mutations, we investigated the efficacy and safety of regimens that included molecularly targeted drugs such as immune checkpoint inhibitors (ICIs) through a network meta-analysis. METHODS: Databases were searched systematically to identify appropriate articles, in which randomized trials with incurable squamous NSCLC were described. Suitable studies were manually checked by two reviewers. A random model network meta-analysis was conducted, in which the primary outcome was the overall survival rate. RESULTS: We identified 48 studies, which included 16 391 patients. When a platinum + third-generation cytotoxic agent regimen (platinum regimen) was a reference, the platinum regimen + pembrolizumab (Pemb) yielded the best results in regard to the overall survival rate when compared with chemotherapy (hazard ratio [HR] = 0.57, 95% confidence interval [CI] = 0.36-0.90, p = 0.016) followed by the platinum regimen + nivolumab (Niv) + ipilimumab (Ipi) (HR = 0.61, 95% CI = 0.44-0.84, p = 0.003). However, the efficacy of ICI monotherapy was not statistically different from that of the platinum regimen. CONCLUSIONS: The combination therapies, which were the platinum regimen + Pemb and the platinum regimen + Niv + Ipi, rather than ICI monotherapy were effective first-line agents for treating squamous NSCLC with low PD-L1 levels.

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Adverse events induced by nivolumab and ipilimumab combination regimens.

Kohei Somekawa, Nobuyuki Horita, Ayami Kaneko, Yoichi Tagami, Nobuhiko Fukuda, Hiromi Matsumoto, Ho Namkoong, Yu Fujiwara, Kaoru Minegishi, Takeshi Fukumoto, Keisuke Watanabe, Yu Hara, Nobuaki Kobayashi, Takeshi Kaneko

Therapeutic advances in medical oncology 14 17588359211058393 - 17588359211058393 2022

ISSN 1758-8340

Background: No meta-analysis has assessed the pooled frequencies of adverse events (AEs) induced by concomitant nivolumab plus ipilimumab regimen for anticancer-medications-naïve malignancies. Furthermore, no meta-analysis has compared detailed safety profiles between four doses of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks (N3I1) and four doses of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (N1I3). Objectives of this study was estimating AE frequencies, and comparison of AE frequencies between N3I1 and N1I3 regimens. Methods: Four major electronic databases were searched; both interventional and observational studies were included. All primary cancer types were permitted. Patients should not have been previously treated with any anti-cancer medications. The frequency of AEs was pooled using a random-model meta-analysis using the generic inverse variance method. Protocol registration: UMIN000044090. Results: Forty articles representing 48 populations with 4,677 patients were included in the study. The pooled frequencies for key indicators were as follows: any AE, 81.3% (95% confidence interval (CI) 77.5-85.1); grade 3 or higher AE, 40.6% (95% CI: 35.7-45.5); serious AE, 32.7% (95% CI: 22.4-43.1); AE leading to discontinuation, 28.3% (95% CI: 23.7-32.8); and treatment-related death, 0.7% (95% CI: 0.4-1.1). AEs with the highest incidence were fatigue (27.9%, 95% CI: 22.6-33.3), followed by diarrhea (26.0%, 95% CI: 21.5-30.5), pruritus (24.6%, 95% CI: 20.3-28.8), rash (24.0% 95% CI: 19.3-28.7), and elevated aspartate aminotransferase (21.2%, 95% CI: 14.9-27.5). Subgroup analyses demonstrated that N3I1, compared to N1I3, less frequently induced any AE (N1I3 95.7%, N3I1 84.5%, p = 0.003), grade 3 or higher AE (N1I3 64.3%, N3I1 35.7%, p < 0.001), and serious AE (N1I3 61.4%, N3I1 47.8%, p = 0.004). Conclusions: Approximately 40% of patients had grade 3 or higher AE. The N3I1 regimen was substantiated to trigger fewer any AEs, high grade AEs, and serious AE than the N1I3 regimen.

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Best regimens for treating chemo‐naïve incurable squamous non‐small cell lung cancer with a programmed death‐ligand 1 tumor proportion score of 1%–49%: A network meta‐analysis

N Fukuda, N Horita, H Namkoong, A Kaneko, K Somekawa, Y Tagami, ...

Thoracic Cancer 13 (1), 84-94 2022

Association between ABO blood group/genotype and COVID-19 in a Japanese population (preprint)

T Kusumoto, S Chubachi, H Namkoong, H Tanaka, H Lee, S Azekawa, ...

2022

Association between ABO blood group/genotype and COVID-19 in a Japanese population

T Kusumoto, S Chubachi, H Namkoong, H Tanaka, H Lee, S Azekawa, ...

2022

Analysis of Adverse Drug Events in Pulmonary Mycobacterium avium Complex Disease Using Spontaneous Reporting System

H Namkoong, T Ozawa, R Takaya, Y Takahashi, K Fukunaga, Y Enoki, ...

2022

Analysis of adverse drug events in pulmonary Mycobacterium avium complex disease using spontaneous reporting system

T Ozawa, H Namkoong, R Takaya, Y Takahashi, K Fukunaga, Y Enoki, ...

BMC infectious diseases 22 (1), 580 2022

Clinical clustering with prognostic implications in Japanese COVID-19 patients: report from Japan COVID-19 Task Force, a nation-wide consortium to investigate COVID-19 host …

S Otake, S Chubachi, H Namkoong, K Nakagawara, H Tanaka, H Lee, ...

BMC Infectious Diseases 22 (1), 735 2022

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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Identification of commensals and molecular components mediating trypsin degradation in the large intestine (preprint)

K Honda, K Atarashi, S Sasajima, Z Wang, K Nishiyama, T Matsunaga, ...

2022

Identification of commensals and molecular components mediating trypsin degradation in the large intestine

K Honda, K Atarashi, S Sasajima, Z Wang, K Nishiyama, T Matsunaga, ...

2022

Estimating immunity with mathematical models for SARS-CoV-2 after COVID-19 vaccination

Y Sato, Y Uwamino, K Nagashima, A Yoshifuji, S Suga, M Nagao, ...

2022

Early-Phase Adverse Effects and Management of Liposomal Amikacin Inhalation for Refractory Mycobacterium avium Complex Lung Disease in Real-World Settings.

Atsuho Morita, Ho Namkoong, Kazuma Yagi, Takanori Asakura, Makoto Hosoya, Hiromu Tanaka, Ho Lee, Takunori Ogawa, Tatsuya Kusumoto, Shuhei Azekawa, Kensuke Nakagawara, Hirofumi Kamata, Makoto Ishii, Koichi Fukunaga, Hiroyuki Ozawa, Naoki Hasegawa

Infection and drug resistance 15 4001 - 4011 2022

ISSN 1178-6973

Purpose: 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.

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Dynamics of antibody responses, cellular immunity, and breakthrough infections among Japanese healthcare workers during the 6 months after receiving two doses of BNT162b2 mRNA …

Y Uwamino, T Kurafuji, K Takato, A Sakai, A Tanabe, M Noguchi, ...

medRxiv, 2022.01. 29.22270052 2022

Development of Rheumatoid Arthritis in Cavitary Mycobacterium avium Pulmonary Disease: A Case Report of Successful Treatment with CTLA4-Ig (Abatacept).

Hiromu Tanaka, Takanori Asakura, Jun Kikuchi, Makoto Ishii, Ho Namkoong, Yuko Kaneko, Koichi Fukunaga, Naoki Hasegawa

Infection and drug resistance 15 91 - 97 2022

ISSN 1178-6973

Background: 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.

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