Language：Japanese   Publisher：(公社)神奈川県医師会  

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The clinical spectrum of COVID-19 includes a wide range of manifestations, from mild symptoms to severe pneumonia. HLA system plays a pivotal role in immune responses to infectious diseases. The purpose of our study was to investigate the association between HLA and COVID-19 severity in a Japanese population. The study included 209 Japanese COVID-19 patients aged ≥20 years. Saliva samples were collected and used to determine the HLA genotype by HLA imputation through genome-wide association analyses. The association between HLA genotype and COVID-19 severity was then evaluated. The allele frequency was compared between patients with respiratory failure (severe group: 91 cases) and those without respiratory failure (non-severe group: 118 cases), categorising the data into three time periods: pre-Omicron epidemic period, Omicron epidemic period, and total period of this study (from January 2021 to May 2023). In comparing the severe and non-severe groups, the frequencies of the HLA-DQA1*01:03 (35.1% vs. 10.5%, odds ratio [OR] = 4.57, corrected p [pc] = 0.041) and -DQB1*06:01 (32.4% vs. 7.9%, OR = 5.54, pc = 0.030) alleles were significantly higher in the severe group during the pre-Omicron epidemic period. During the Omicron epidemic period, HLA-DQB1*06 (32.4% vs. 7.9%, OR = 5.54, pc = 0.030) was significantly higher in the severe group. During total period of this study, HLA-DQA1*01:03 (30.2% vs. 14.4%, OR = 2.57, corrected pc = 0.0013) and -DQB1*06:01 (44.5% vs. 26.7%, OR = 2.20, pc = 0.013) alleles were significantly higher in the severe group. HLA-DQB1*06:01 and -DQA1*01:03 were in strong linkage disequilibrium with each other (r2 = 0.91) during total period of this study, indicating that these two alleles form a haplotype. The frequency of the HLA-DQA1*01:03-DQB1*06:01 in the severe group was significantly higher than in the non-severe group during pre-Omicron epidemic period (32.4% vs. 7.9%, OR = 5.59, pc = 0.00072), and total period of this study (28.6% vs. 13.1%, OR = 2.63, pc = 0.0013). During Omicron epidemic period, the haplotype did not demonstrate statistical significance, although the odds ratio indicated a value greater 1. Frequencies of the HLA-DQA1*01:03 and -DQB1*06:01 alleles were significantly higher in severe COVID-19 patients, suggesting that these alleles are risk factors for severe COVID-19 pneumonia in the Japanese population.

DOI： 10.1111/tan.15609

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BACKGROUND: For advanced non-small cell lung cancer (NSCLC), combination therapies including a PD-1 inhibitor plus chemotherapy or a PD-1 inhibitor, CTLA-4 inhibitor, and chemotherapy are standard first-line options. However, data directly comparing these regimens are lacking. This study compared the efficacy of pembrolizumab plus chemotherapy (CP) against nivolumab plus ipilimumab and chemotherapy (CNI) in a real-world setting. METHODS: In this multicenter retrospective study, we compared the efficacy and safety of CP and CNI as first-line therapies in 182 patients with stage IIIB-IV NSCLC. Primary outcomes were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included the response rate (RR) and safety profiles. Kaplan-Meier survival curves and Cox proportional hazards models were utilized for data analysis, adjusting for confounding factors such as age, gender, and PD-L1 expression. RESULTS: In this study, 160 patients received CP, while 22 received CNI. The CP group was associated with significantly better PFS than the CNI group (median 11.7 vs. 6.6 months, HR 0.56, p = 0.03). This PFS advantage persisted after propensity score matching to adjust for imbalances. No significant OS differences were observed. Grade 3-4 adverse events occurred comparably, but immune-related adverse events were numerically more frequent in the CNI group. CONCLUSIONS: In real-world practice, CP demonstrated superior PFS compared with CNI. These findings can inform treatment selection in advanced NSCLC.

DOI： 10.1111/1759-7714.15304

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BACKGROUND: Combining multiple tumor markers increases sensitivity for lung cancer diagnosis in the cost of false positive. However, some would like to check as many as tumor markers in the fear of missing cancer. We though to propose a panel of fewer tumor markers for lung cancer diagnosis. METHODS: Patients with suspected lung cancer who simultaneously underwent all six tests [carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA), squamous cell carcinoma-associated antigen (SCC), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), and sialyl Lewis-X antigen (SLX)] were included. Tumor markers with significant impact on the lung cancer in a logistic regression model were included in our panel. Area under the curve (AUC) was compared between our panel and the panel of all six. RESULTS: We included 1,733 [median 72 years, 1,128 men, 605 women, 779 (45%) confirmed lung cancer]. Logistic regression analysis suggested CEA, CYFRA, and NSE were independently associated with the lung cancer diagnosis. The panel of these three tumor markers [AUC =0.656, 95% confidence interval (CI): 0.630-0.682, sensitivity 0.650, specificity 0.662] had better (P<0.001) diagnostic performance than six tumor markers (AUC =0.575, 95% CI: 0.548-0.602, sensitivity 0.829, specificity 0.321). CONCLUSIONS: Compared to applying all six markers (at least one marker above the upper limit of normal), the panel with three markers (at least one marker above the upper limit of normal) led to a better predictive value by lowering the risk of false positives.

DOI： 10.21037/tlcr-23-855

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The ILD-GAP scoring system is known to be useful in predicting prognosis in patients with interstitial lung disease (ILD). An elevated monocyte count was associated with increased risks of IPF poor prognosis. We examined whether the ILD-GAP scoring system combined with the monocyte ratio (ILD-GAPM) is superior to the conventional ILD-GAP model in predicting ILD prognosis. METHODS: In patients with ILD treated between April 2013 and April 2017, we were retrospectively assessed the relationships between baseline clinical parameters, including age, sex, Charlson Comorbidity Index score (CCIS), ILD diagnosis, blood biomarkers, pulmonary function test results, and disease outcomes. In ILD patients were included idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (iNSIP), collagen vascular disease-related interstitial pneumonia (CVD-IP), chronic hypersensitivity pneumonitis (CHP), and unclassifiable ILD (UC-ILD). We also assessed the ability to predict prognosis was compared between the ILD-GAP and ILD-GAPM models. RESULTS: A total of 179 patients (mean age, 73 years) were assessed. All of them were taken pulmonary function test, including percentage predicted diffusion capacity for carbon monoxide. ILD patients included 56 IPF cases, 112 iNSIP and CVD-IP cases, 6 CHP cases and 5 UC-ILD cases. ILD-GAPM provided a greater area under the receiver-operating characteristic curve (0.747) than ILD-GAP (0.710) for predicting 3-year ILD-related events. Furthermore, the log-rank test showed that the Kaplan-Meier curves in ILD-GAPM were significantly different by stage (P = 0.015), but not by stage in ILD-GAP (P = 0.074). CONCLUSIONS: The ILD-GAPM model may be a more accurate predictor of prognosis for ILD patients than the ILD-GAP model.

DOI： 10.1186/s12890-023-02833-6

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved outcomes in cancer treatment but are also associated with adverse events and financial burdens. Identifying accurate biomarkers is crucial for determining which patients are likely to benefit from ICIs. Current markers, such as PD-L1 expression and tumor mutation burden, exhibit limited predictive accuracy. This study utilizes a Clinical Data Warehouse (CDW) to explore the prognostic significance of novel blood-based factors, such as the neutrophil-to-lymphocyte ratio and red cell distribution width (RDW), to enhance the prediction of ICI therapy benefit. METHODS: This retrospective study utilized an exploratory cohort from the CDW that included a variety of cancers to explore factors associated with pembrolizumab treatment duration, validated in a non-small cell lung cancer (NSCLC) patient cohort from electronic medical records (EMR) and CDW. The CDW contained anonymized data on demographics, diagnoses, medications, and tests for cancer patients treated with ICIs between 2017-2022. Logistic regression identified factors predicting ≤2 or ≥5 pembrolizumab doses as proxies for progression-free survival (PFS), and Receiver Operating Characteristic analysis was used to examine their predictive ability. These factors were validated by correlating doses with PFS in the EMR cohort and re-testing their significance in the CDW cohort with other ICIs. This dual approach utilized the CDW for discovery and EMR/CDW cohorts for validating prognostic biomarkers before ICI treatment. RESULTS: A total of 609 cases (428 in the exploratory cohort and 181 in the validation cohort) from CDW and 44 cases from EMR were selected for study. CDW analysis revealed that elevated red cell distribution width (RDW) correlated with receiving ≤2 pembrolizumab doses (p = 0.0008), with an AUC of 0.60 for predicting treatment duration. RDW's correlation with PFS (r = 0.80, p<0.0001) and its weak association with RDW (r = -0.30, p = 0.049) were confirmed in the EMR cohort. RDW also remained significant in predicting short treatment duration across various ICIs (p = 0.0081). This dual methodology verified pretreatment RDW elevation as a prognostic biomarker for shortened ICI therapy. CONCLUSION: This study suggests the utility of CDWs in identifying prognostic biomarkers for ICI therapy in cancer treatment. Elevated RDW before treatment initiation emerged as a potential biomarker of shorter therapy duration.

DOI： 10.1371/journal.pone.0299760

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BACKGROUND: Biologics are the important drugs for severe asthma, but clinical trials included few elderly patients. Data on the safety and efficacy of benralizumab in elderly asthma patients are limited. METHODS: This clinical study was a multicentre, retrospective, observational study at two hospitals. Patients aged ≥18 years diagnosed with severe asthma treated with benralizumab were included. Elderly patients were defined as those aged 70 years or older. Efficacy and safety were then analyzed in elderly and non-elderly patients. The primary endpoints were the annual number of asthma exacerbations for efficacy and the discontinuation rate due to adverse events for safety. RESULTS: Between August 2016 and October 2022, 61 patients were enrolled; 10 patients were excluded, and 51 (22 elderly, 29 non-elderly) patients were analyzed. In elderly patients, the annual number of asthma exacerbations before treatment with benralizumab (pre-benralizumab) was 3.78, and the number during treatment with benralizumab was 1.26, a decrease of 2.52 (95% confidence interval [CI], 1.3 to 3.74, p < 0.001). In non-elderly patients, the annual number of asthma exacerbation in the pre-benralizumab period was 3.24, and during treatment with benralizumab it was 0.68, a decrease of 2.56 (95% CI, 1.3 to 3.82, p < 0.001). There was no significant difference in discontinuation due to treatment-related adverse events (elderly vs non-elderly, 2 (9%) vs 0 (0%), p = 0.18). CONCLUSION: Benralizumab reduced the annual number of asthma exacerbations and was well tolerated in elderly patients.

DOI： 10.1080/20018525.2024.2384173

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INTRODUCTION: Total baseline tumor size (BTS) is a prognostic factor for programmed death 1 and programmed death-ligand 1 (PD-L1) inhibitor treatments. However, the prognostic value of total BTS for patients with small-cell lung cancer (SCLC) who receive chemotherapy plus PD-L1 inhibitor remains unknown. Thus, in this study, we aimed to determine whether total BTS is associated with prognosis in patients with SCLC who receive chemotherapy plus PD-L1 inhibitor as first-line therapy. METHODS: This study included patients with extensive-stage SCLC or post-chemoradiotherapy recurrence of limited-stage SCLC who received chemotherapy plus PD-L1 inhibitor as first-line therapy from August 2019 to December 2022. The two lesions with the largest diameter among the measurable lesions in each organ were selected from up to five organs (maximum of 10 lesions), and the sum of all diameters was defined as total BTS. The patients were divided into two groups, large or small, with total BTS using X-tile software. Median survival was analyzed using the Kaplan-Meier method, and the groups were compared using the log-rank test. Univariate and multivariate analyses examined the association between total BTS and prognosis. RESULTS: Fifty patients were included; 14% had large total BTS (>183.2 mm) and 86% had small total BTS (≤183.2 mm). The median observation period was 10.5 months. The large total BTS group showed significantly worse overall survival than the small total BTS group (median: 26.8 months vs. 5.7 months, P = 0.0003). The multivariate analysis indicated that large total BTS was an independent negative predictor of overall survival (hazard ratio: 7.14, 95% confidence interval: 1.89-26.96). DISCUSSION: Total BTS is a potentially useful prognostic factor for patients with advanced SCLC who receive chemotherapy plus PD-L1 inhibitor as first-line therapy.

DOI： 10.3389/fonc.2024.1400277

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Serum heme oxygenase (HO)-1 level has been reported as a clinically reliable diagnostic biomarker for acute exacerbation of interstitial lung disease (ILD); however, its utility for predicting mortality among these patients is unclear. Serum HO-1 levels of patients newly diagnosed with acute exacerbation of ILD were measured at the time of initiating steroid pulse therapy. The relationship between serum HO-1 and various other serum biomarkers, change in HRCT findings, and disease prognosis at 12 weeks after diagnosis of acute exacerbation was evaluated in 51 patients, of whom 17 (33%) had idiopathic pulmonary fibrosis (IPF). Serum HO-1 was higher in patients with acute exacerbation of IPF than in patients with acute exacerbation of other ILDs. Serum HO-1 levels were higher in patients who died within these 12 weeks than in survivors. Among age, sex, comorbidities, IPF diagnosis, HRCT findings, and blood biomarkers, serum HO-1 was a primary predictor of 12-week mortality. In 41 patients who underwent repeat HRCT, serum HO-1 was higher in patients with honeycomb progression than in those without. Serum HO-1 measurement could be useful for evaluating disease mortality and morbidity of patients with acute exacerbation of ILDs.

DOI： 10.1038/s41598-023-49342-4

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BACKGROUND: For simultaneous prediction of phenotypic drug susceptibility test (pDST) for multiple anti-tuberculosis drugs, the whole genome sequencing (WGS) data can be analyzed using either catalogue-based approach, wherein one causative mutation suggests resistance, (e.g., WHO catalog) or non-catalogue-based approach using complicated algorithm (e.g., TB-profiler, machine learning). The aim was to estimate the predictive ability of WGS-based tests with pDST as the reference, and to compare the two approaches. METHODS: Following the systematic literature search, the diagnostic test accuracies for 14 drugs were pooled using a random-effect bivariate model. RESULTS: Out of 779 articles, 44 articles with 16,821 specimens for meta-analysis and 13 articles not for meta-analysis were adopted. The areas under summary receiver operating characteristic curve suggested "excellent" (0.97-1.00) for 2 drugs (isoniazid 0.975, rifampicin 0.975), "very good" (0.93-0.97) for 8 drugs (pyrazinamide 0.946, streptomycin 0.952, amikacin 0.968, kanamycin 0.963, capreomycin 0.965, para-aminosalicylic acid 0.959, levofloxacin 0.960, ofloxacin 0.958), and "good" (0.75-0.93) for 4 drugs (ethambutol 0.926, moxifloxacin 0.896, ethionamide 0.878, prothionamide 0.908). The non-catalogue-based and catalogue-based approaches had similar ability for all drugs. CONCLUSION: WGS accurately identifies isoniazid and rifampicin resistance. For most drugs, positive WGS results reliably predict pDST positive. The two approaches had similar ability.

DOI： 10.1093/infdis/jiad480

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Language：Japanese   Publisher：(一社)日本呼吸器内視鏡学会  

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BACKGROUND: This study aims to assess the real-world impact of advancements in first-line systemic therapies for non-small-cell lung cancer (NSCLC), focusing on the role of driver gene mutations and programmed death-ligand 1 (PD-L1) expression levels. METHODS: Conducted across eight medical facilities in Japan, this multicenter, retrospective observational research included 863 patients diagnosed with NSCLC and treated between January 2015 and December 2022. The patients were categorized based on the type of systemic therapy received: cytotoxic agents, molecular targeting agents, immune checkpoint inhibitors, and combination therapies. Comprehensive molecular and immunohistochemical analyses were conducted, and statistical evaluations were performed. RESULTS: The median overall survival (OS) shows significant variations among treatment groups, with targeted therapies demonstrating the longest OS. This study also revealed that high PD-L1 expression was common in the group treated with immune checkpoint inhibitors. Multivariate analysis was used to identify the type of anticancer drug and the expression of PD-L1 at diagnosis as the impactful variables affecting 5-year OS. CONCLUSIONS: This study underscores the efficacy of targeted therapies and the critical role of comprehensive molecular diagnostics and PD-L1 expression in affecting OS in NSCLC patients, advocating for their integration into routine clinical practice.

DOI： 10.3390/cancers15215248

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BACKGROUND: The efficacy of adding atezolizumab to the platinum doublet regimen for extensive disease small cell lung cancer (ED-SCLC) remains marginally limited. METHODS: We retrospectively assessed the real-world efficacy and safety of atezolizumab in addition to carboplatin and etoposide (EP + A), versus carboplatin and etoposide (EP) alone in previously untreated ED-SCLC patients. RESULTS: From a total of 99 patients, 46 were assigned to the EP + A group, and 53 to the EP group. No significant difference was observed in progression-free survival between the groups. However, the overall survival (OS) was significantly longer in the EP + A group (20.8 vs 12.1 months; HR: 0.52; p = 0.0127). Patients older than 70 years, male, with performance status 0-1, without liver metastasis, and low levels of C-reactive protein and neutrophil-lymphocyte ratio, experienced longer OS in the EP + A group compared to the EP group. CONCLUSION: The addition of atezolizumab to the platinum doublet regimen significantly extended OS in ED-SCLC patients, particularly among certain subgroups, suggesting its potential value in personalized treatment strategies. Further investigation is warranted to validate these findings.

DOI： 10.1007/s00432-023-05457-9

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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BACKGROUND: Personalized treatment for non-small cell lung cancer (NSCLC) has advanced rapidly, and elucidating the genetic changes that trigger this disease is crucial for appropriate treatment selection. Both slow-pull and aspiration methods of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are accepted methods for collecting samples suitable for next-generation sequencing (NGS) to examine driver gene mutations and translocations in NSCLC. Here, we aimed to determine which of these two methods is superior for obtaining higher-quality samples from patients with NSCLC. METHODS: Seventy-one patients diagnosed with NSCLC via EBUS-TBNA using the slow-pull or aspiration (20-mL negative pressure) methods between July 2019 and September 2022 were included. A total of 203 tissue samples from the 71 patients were fixed in formalin, embedded in paraffin, and mounted on slides. The presence of tissue cores, degree of blood contamination, and number of tumor cells were compared between the groups. The success rate of NGS, using Oncomine Dx Target Test Multi-CDx, was also compared between the groups. RESULTS: The slow-pull method was associated with a higher yield of tissue cores, lower degree of blood contamination, and higher number of tumor cells than the aspiration method. The success rate of the NGS was also significantly higher for the slow-pull group (95%) than for the aspiration group (68%). CONCLUSION: Overall, these findings suggest that the slow-pull method is a superior technique for EBUS-TBNA to obtain high-quality tissue samples for NGS. The slow-pull method may contribute to the identification of driver gene mutations and translocations and facilitate personalized treatment of NSCLC.

DOI： 10.1002/cam4.6561

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INTRODUCTION: Tuberculosis (TB) remains a leading cause of death globally. Identifying the factors associated with mortality during hospitalization for TB is crucial for improving patient outcomes. This study aimed to investigate the potential risk factors, including T-SPOT.TB test results and routine laboratory markers of inflammation, associated with death during hospitalization due to TB. METHODS: A retrospective analysis was conducted on 244 hospitalized TB patients. Demographic data, clinical characteristics, T-SPOT.TB results, and laboratory parameters were collected. Univariate and multivariate analyses were performed to identify independent risk factors for in-hospital mortality. RESULTS: Among the patients, 206 survived and 38 died during hospitalization. Multivariate analysis revealed that age (HR: 1.08, 95% CI: 1.02-1.15, p = 0.001), a negative T-SPOT.TB test result (HR: 4.01, 95% CI: 1.78-9.01, p < 0.001), elevated C-reactive protein (CRP) levels (HR: 1.04, 95% CI: 1.01-1.08, p = 0.007), and increased neutrophil-to-lymphocyte ratio (NLR) (HR: 1.04, 95% CI: 1.00-1.07, p = 0.025) were independent risk factors for mortality. CONCLUSIONS: This study identified age, a negative T-SPOT.TB result, elevated CRP levels, and a high NLR as significant independent risk factors for death in hospitalized TB patients. These findings underscore the importance of these parameters in the risk stratification and management of hospitalized TB patients. Further research is warranted to elucidate the mechanisms behind these associations and to validate these results in different populations.

DOI： 10.1016/j.jiac.2023.09.011

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Language：Japanese   Publisher：日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会  

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Language：Japanese   Publisher：日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会  

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BACKGROUND: Based on the results of the PACIFIC trial, maintenance with durvalumab has emerged as the standard treatment following concurrent chemoradiotherapy in patients with unresectable locally advanced non-small cell lung carcinoma (NSCLC). However, adverse events attributed to durvalumab, especially lung injuries, including immune-related adverse events, and radiation pneumonitis, are concerning. This study retrospectively investigated the factors related to lung injury in patients receiving the PACIFIC regimen. METHODS: Patients with unresectable locally advanced NSCLC who received durvalumab maintenance therapy following concurrent chemoradiotherapy at Yokohama City University Medical Centre between July 2018 and March 2022 were included. Clinical data, volume of normal lung receiving 20 or 5 Gy or more (V20 or V5), planning target volume (PTV), and relative lung parenchyma volume in emphysematous lung receiving 20 or 5 Gy or more (RLPV20 or 5; V20 or V5/100-percentage of low-attenuation volume) were evaluated. RESULTS: Performance status (PS), V20, V5, PTV, RLPV20, and RLPV5 were significantly higher in the lung injury group in the univariate analysis. Furthermore, RLPV20 was the most significant factor in the lung injury group in the multivariate analysis comprising PS, PTV, V20, and RLPV20. CONCLUSION: RLPV20 and RLPV5 are useful in estimating lung inflammation. RLPV20 could be considered the most reliable risk factor for maintenance therapy with durvalumab following concurrent chemoradiotherapy in patients with unresectable locally advanced NSCLC.

DOI： 10.1111/1759-7714.15042

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Acute exacerbation (AE) of interstitial pneumonia (IP) shows poor prognosis, due to the typical histological pattern of diffuse alveolar damage superimposed upon lung fibrosis. The previous reports comparing clinical features between AE of idiopathic interstitial pneumonias (IIPs) and those of IPs with known etiology are limited. We retrospectively compared clinical parameters including age, sex, Charlson Comorbidity Index score (CCIS), blood biomarkers at diagnosis of AE, treatment, and 3-month mortality between patients with AE of IIPs and collagen vascular disease-associated interstitial pneumonia (CVD-IP). We assessed 85 patients, comprising 66 patients with AE of IIPs (78%) and 19 patients with AE of CVD-IP (22%). The least absolute shrinkage and selection operator regression selected CCIS (hazard ratio, 1.281; 95% confidence interval, 1.055-1.556; P = 0.012) and log serum lactate dehydrogenase (LDH) (hazard ratio, 6.267; 95% confidence interval, 2.172-18.085; P < 0.001) as significant predictors of 3-month mortality among these patients. Also, the adjusted survival curves using sex, CCIS, and serum LDH showed no significant differences between these two groups. In conclusion, among AE patients, CCIS and serum LDH level may be more important prognostic factors for 3-month mortality rather than two classification of IP subtypes: IIPs and CVD-IP.

DOI： 10.18999/nagjms.85.3.602

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DOI： 10.1002/cam4.6405

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(一社)日本結核・非結核性抗酸菌症学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The clinical features of asthma with connective tissue diseases (CTDs) are not well-known. This study therefore aimed to investigate the clinical characteristics of asthma with CTDs. METHODS: We retrospectively examined the records of adults (≥18 years old) with asthma followed up between January 2010 and December 2019. We then compared the clinical features of asthma with and without CTDs. RESULTS: Among 568 subjects with asthma, 42 subjects (7.4%) had CTDs. The most frequent concomitant CTD was rheumatoid arthritis (n = 23, 54.8%), followed by systemic lupus erythematosus (n = 6, 14.3%). The proportion of women (with vs. without CTDs, 85.7% vs. 56.5%, p < 0.001) and Global Initiative for Asthma step were higher (Step 4 or 5, with vs. without CTDs, 81.0% vs. 62.0%, p = 0.01) in asthma with CTDs, whereas frequency of allergic rhinitis was higher in asthma without CTDs (with vs. without CTDs, 7.1% vs. 26.1%, p = 0.005). Eosinophil ratio (with vs. without CTDs, 2.1% vs. 3.5%, p = 0.009) and total immunoglobulin E level (with vs. without CTDs, 43 IU/mL vs. 237 IU/mL, p = 0.002) were lower in asthma with CTDs. In terms of lung function, percentage predicted forced vital capacity (with vs. without CTDs, 86.7% vs. 99.7%, p = 0.008) and percentage predicted forced expiratory volume in 1 s (%FEV1) (with vs. without CTDs, 77.2% vs. 88.4%, p = 0.02) were all lower in asthma with CTDs. With multivariable analysis, CTDs (odds ratio [OR] 2.8, 95%CI 1.3-6.0; p = 0.008), chronic obstructive pulmonary disease (OR 3.8, 95%CI 2.1-6.7; p < 0.001) and asthma onset at <20 years old (OR 1.8, 95%CI 1.1-3.2; p = 0.03) were associated with low FEV1 (defined as %FEV1 < 80%) in asthma. CONCLUSIONS: Asthma with CTDs was related to lower lung function and low-T2 inflammation asthma.

DOI： 10.1111/crj.13595

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are extensively used in the treatment of non-small cell lung cancer (NSCLC); hence, equal access to them is important. Therefore, this study aimed to identify regional differences in the prescription of EGFR-TKIs and the factors contributing to these differences. In this ecological study, we collected data using the National Database Open Data and the National Cancer Registry. The standardized claim ratio (SCR) was used as an indicator of the number of EGFR-TKI prescriptions. Additionally, we examined the association between SCR and various factors to identify the factors associated with this difference. The average SCR for the top three provinces was 153.4, while the average for the bottom three provinces was 61.6. Multivariate analysis used for evaluating the association of SCR with variables revealed that the number of designated cancer hospitals and radiation therapies were independent factors associated with the SCR of EGFR-TKIs. There were significant regional differences in the prescriptions of EGFR-TKIs in Japan based on the number of coordinated designated cancer hospitals and the number of patients receiving radiotherapy alone. These findings emphasize the need to implement policies to increase the number of hospitals to reduce regional differences.

DOI： 10.1038/s41598-023-31856-6

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Other Link： https://www.nature.com/articles/s41598-023-31856-6

Language：English  

Primary tracheal small-cell carcinoma is rare, and is often treated using small-cell lung cancer guidelines given that no standard treatment has been established for it. We report a patient in whom nodules appeared in the trachea and left main bronchus 11 months after surgery for pulmonary large-cell neuroendocrine carcinoma; a biopsy revealed small-cell carcinoma. Given the absence of malignant lesions elsewhere in the body, the lesions were diagnosed as primary tracheal small-cell carcinoma. Respiratory failure progressed rapidly owing to airway stenosis caused by the growing lesion, and the patient required nasal high-flow therapy. However, the lesions shrank a few days after commencing first-line chemotherapy, and his respiratory failure resolved. Accelerated hyperfractionated radiotherapy was administered in conjunction with the third course of chemotherapy, and the patient ultimately achieved a complete response. Although the lesions were initially suspected of being postoperative recurrence of pulmonary large-cell neuroendocrine carcinoma, the fact that the biopsy revealed them to be primary tracheal small-cell carcinoma indicates that intra-airway nodules that appear after lung cancer surgery may possibly be primary tracheal tumors.

DOI： 10.1111/1759-7714.14860

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Language：English  

Thymic neuroendocrine tumors associated with multiple endocrine neoplasia are only defined as carcinoid and are not associated with large-cell neuroendocrine carcinoma (LCNEC). We report the case of a multiple endocrine neoplasia type 1 patient with atypical carcinoid tumors with elevated mitotic counts (AC-h), an intermediate condition between carcinoid and LCNEC. A 27-year-old man underwent surgery for an anterior mediastinal mass and was diagnosed with thymic LCNEC. Fifteen years later, a mass appeared at the same site, which was determined to be a postoperative recurrence based on the pathological results of a needle biopsy and the clinical course. The patient's disease remained stable for 10 months on anti-programmed death-ligand 1 antibody and platinum-containing chemotherapy. The needle biopsy specimen was submitted for next-generation sequencing, which revealed a MEN1 gene mutation, and after further examination, a diagnosis of multiple endocrine neoplasia type 1 was made. A re-examination of the surgical specimen from 15 years prior showed that it corresponded to AC-h. Although thymic AC-h is classified as thymic LCNEC according to the current definition, our data suggests that a search for multiple endocrine neoplasia is warranted in such patients.

DOI： 10.1111/1759-7714.14863

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The ILD-GAP scoring system has been widely used to predict the prognosis of patients with interstitial lung disease (ILD). The ability of the ILD-GAP scoring system combined with the Charlson Comorbidity Index score (CCIS) (ILD-GAPC) to predict ILD prognosis was investigated. METHODS: In ILD patients, including idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (iNSIP), collagen vascular disease-related interstitial pneumonia (CVD-IP), chronic hypersensitivity pneumonitis (CHP), and unclassifiable ILD (UC-ILD), treated between April 2013 and April 2017, the relationships between baseline clinical parameters, including age, sex, CCIS, ILD diagnosis, pulmonary function test results, and disease outcomes, were retrospectively assessed, and the ability to predict prognosis was compared between the ILD-GAP and ILD-GAPC models, respectively. RESULTS: A total of 185 patients (mean age, 71.9 years), all of whom underwent pulmonary function testing, including percentage predicted diffusion capacity for carbon monoxide, were assessed. ILD diagnosis consisted of IPF in 57 cases, iNSIP and CVD-IP in 117 cases, CHP in 6 cases, and UC-ILD in 5 cases. The ILD-GAPC provided a greater area under the receiver operating characteristic curve (0.758) for predicting 3-year ILD-related events than the ILD-GAP (0.721). In addition, log-rank tests showed that the Kaplan-Meier curves differed significantly among low, middle, and high ILD-GAPC scores (P < 0.001), unlike ILD-GAP scores (P = 0.083). CONCLUSIONS: The ILD-GAPC model could provide more accurate information for predicting prognosis in patients with ILD than the ILD-GAP model.

DOI： 10.1155/2023/5088207

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown remarkable therapeutic outcomes among cancer patients. Durvalumab plus tremelimumab (DT) is under investigation as a new ICI combination therapy, and its efficacy has been reported in various types of cancer. However, the safety profile of DT remains unclear, especially considering rare adverse events (AEs). OBJECTIVE: We aimed to assess the frequency of AEs associated with DT. DESIGN: This study type is a systematic review and meta-analysis. DATA SOURCES AND METHODS: Four databases were searched for articles. Randomized trials, single-arm trials, and prospective and retrospective observational studies were included. The type of cancer, previous treatment, and performance status were not questioned. Major AE indicators such as any AE and the pooled frequency of each specific AE were used as outcomes. As a subgroup analysis, we also compared cases in which DT was performed as first-line treatment with those in which it was performed as second-line or later treatment. The protocol for this systematic review was registered on the University Hospital Medical Information Network (UMIN) Center website (ID: UMIN000046751). RESULTS: Forty-one populations including 3099 patients were selected from 30 articles. Pooled frequencies of key AE indicators are shown below: any AEs, 77.8% [95% confidence interval (CI): 67.9-87.6]; grade ⩾ 3 AEs, 29.3% (95% CI: 24.2-34.4); serious AEs, 34.9% (95% CI: 28.1-41.7); AE leading to discontinuation, 13.3% (95% CI: 9.3-17.4); treatment-related deaths, 0.98% (95% CI: 0.5-1.5). AEs with a frequency exceeding 15% are shown below: fatigue, 30.1% (95% CI: 23.8-36.3); diarrhea, 21.7% (95% CI: 17.8-25.6); pruritus 17.9% (95% CI: 14.4-21.3); decreased appetite, 17.7% (95% CI: 13.7-22.0); nausea, 15.6% (95% CI: 12.1-19.6). There were no significant differences in these pooled frequencies between subgroups. CONCLUSIONS: The incidence of any AE in DT therapy was approximately 78%, and the incidence of grade 3 or higher AEs was approximately 30%, which was independent of prior therapy.

DOI： 10.1177/17588359231198453

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Among patients with idiopathic pulmonary fibrosis (IPF), few studies have investigated the clinical impact of anti-fibrotic treatment (AFT) with and without comorbidities. The aim of the study was to determine whether Charlson Comorbidity Index score (CCIS) can predict the efficacy of AFT in patients with IPF. METHODS: We retrospectively assessed data extracted from the medical records of IPF patients who received anti-fibrotic agents between 2009 and 2019. The collected data included age, sex, CCIS, pulmonary function test, high-resolution computed tomography (HRCT) pattern, gender/age/physiology (GAP) score, and 3-year IPF-related events defined as the first acute exacerbation or death within 3 years after starting AFT. RESULTS: We assessed 130 patients (median age, 74 years) who received nintedanib (n = 70) or pirfenidone (n = 60). Median duration of AFT was 425 days. Patients were categorized into high (≥ 3 points) and low (≤ 2 points) CCIS groups. There was no significant difference between the groups in terms of age, sex, duration of AFT, GAP score, or incidence of usual interstitial pneumonia pattern on HRCT except percentage predicted diffusion capacity of lung for carbon monoxide. Also, significant difference was not seen between the groups for 3-year IPF-related events (P = 0.75). Especially, in the low CCIS group but not the high CCIS group, the longer duration of AFT had better disease outcome. CONCLUSION: In the present study, we could not show any relation between CCIS and IPF disease outcomes in patients undergoing AFT, though the longer duration of AFT might be beneficial for IPF outcomes among patients with low CCIS.

DOI： 10.1371/journal.pone.0291489

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OBJECTIVE: The manifestations of sarcoidosis differ by ethnicity and region. However, the few studies that have focused on elderly sarcoidosis are only from Western countries. Therefore, we investigated elderly sarcoidosis in Japan. METHODS: We retrospectively reviewed the records of adult patients (≥18 years old) who were diagnosed with sarcoidosis from 1 April 2006 to 31 March 2020. The diagnosis was pathologically confirmed in all patients. We compared the clinical features of elderly (diagnosed at ≥65 years old) and non-elderly (diagnosed at <65 years old) patients. RESULTS: Thirty-five (33%) of 106 patients were elderly. The elderly group had significantly more comorbidities than the non-elderly group (median [range], 1 [0-4] vs. 0 [0-5]). The biopsy site at diagnosis included significantly more extrathoracic sites in the elderly than non-elderly group (57.1% vs. 33.8%). The elderly group had significantly more muscle lesions than the non-elderly group at the time of diagnosis (11.4% vs. 1.4%) and at any time during follow-up (17.1% vs. 1.4%). CONCLUSION: In Japan, elderly patients with sarcoidosis might have more muscle involvement and comorbidities than younger patients. Because comorbidities might affect the prognosis of elderly sarcoidosis, further study is needed to clarify the effect of comorbidities on elderly sarcoidosis.

DOI： 10.1177/03000605221142705

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(一社)日本呼吸器内視鏡学会  

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BACKGROUND: This study aimed to determine the effectiveness of liquid biopsy in detecting epidermal growth factor receptor (EGFR) mutations at diagnosis, disease progression, and intermediate stages. METHODS: This prospective, multicenter, observational study included 30 patients with non-small cell lung cancer treated with afatinib, harboring a major EGFR mutation confirmed by tumor tissue biopsy. We collected blood samples for liquid biopsy at diagnosis, intermediate stage, and progressive disease. Tissue and liquid biopsies were examined using Cobas ® EGFR Mutation Test v2. RESULTS: Liquid biopsy detected EGFR mutations in 63.6% of the patients at diagnosis. The presence of metastasis in the extrathoracic, brain, and adrenal glands correlated positively with the detection of EGFR mutations. Patients with positive EGFR mutations at diagnosis had significantly shorter overall and progression-free survival than patients with negative EGFR mutations. Four of the 18 patients (22.2%) who reached progressive disease had positive EGFR T790M mutations. Three of 10 patients (30.0%) with progressive disease were positive and negative for T790M using tumor re-biopsy and liquid biopsy, respectively. The results of EGFR mutation by tissue re-biopsy were the same as those of liquid biopsy in the three patients who were positive for significant EGFR mutations but negative for the T790M mutation using liquid biopsy at progressing disease. Only two patients were positive for major EGFR mutations at intermediate levels. CONCLUSIONS: Liquid biopsy can be a prognostic factor in EGFR-tyrosine kinase inhibitor treatments at diagnosis. Tumor re-biopsy can be omitted in patients with positive EGFR mutations by liquid biopsy at PD.

DOI： 10.1186/s12885-022-10135-z

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Language：Japanese   Publisher：日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会  

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Language：Japanese   Publisher：日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会  

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/1759-7714.14608

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1759-7714.14608

Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：English   Publishing type：Research paper (scientific journal)  

The present study aimed to evaluate whether serum heme oxygenase (HO)-1 could be a reliable blood biomarker for diagnosing acute exacerbations (AEs) of both idiopathic interstitial pneumonia (IIP) and secondary interstitial pneumonia (SIP). Serum HO-1 levels of newly diagnosed patients with IP were measured, and the relationships between serum HO-1 and other serum biomarkers and high-resolution CT scores, were evaluated. Blood samples were collected from 90 patients with IIP, including 32 having an AE, and 32 with SIP, including 9 having an AE. The patients having an AE had significantly higher HO-1 levels than those not having an AE (35.2 ng/mL vs. 16.4 ng/mL; p < 0.001). On receiver operating characteristics (ROC) curve analysis for serum HO-1 ability to detect an AE, the area under the ROC curve (AUC) was 0.87 in patients with IIPs and 0.86 in those with SIPs. Also, in patients with both IIPs and SIPs, the combination of the serum HO-1 level and the GGO score showed favorable AUCs (IIPs: 0.92, SIPs: 0.83), though HO-1-not-including model (combination of LDH and GGO) also showed acceptable AUCs. Serum HO-1 could be a clinically useful biomarker for the accurate diagnosis of patients with AEs.

DOI： 10.1038/s41598-022-17290-0

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BACKGROUND: Multiplex gene-panel tests have recently been developed, including the Oncomine Dx Target Test multi-CDx system (ODxTT), and are commonly used to determine the adaptation of molecular-targeting drugs in non-small cell lung cancer. However, in actual clinical settings, we obtain false results owing to the small biopsy samples. We aimed to optimize tissue preparation methods to improve the success rate. PATIENTS AND METHODS: We investigated 88 biopsy samples. The area and nucleated cell count in the first cut section were quantified using a morphometric software. Pathological parameters, including "total tissue area" and "total nucleated cell count," were calculated by multiplying the total number of slides submitted to ODxTT. Optimal cutoff values to obtain the best success rate were also determined. Additionally, we morphometrically measured actual tumor cell proportions and attempted to determine the lower limit possible to detect mutations. RESULTS: Optimal cutoff values for "total nucleated cell count" and "total tissue area" were 132,885 and 32.94 mm2, respectively. The actual tumor cell proportions ranged from 4.6 to 97.7%. Even in cases with actual tumor cell proportions of less than 20% (ranging from 4.6 to 19.7%), there was no false negative. CONCLUSION: Thus, we proposed the pathological criteria for accurate ODxTT. Our result suggested that tumor cell proportions of less than 20% (around 5%) could be applicable for ODxTT. We hope that our results will help pathologists to choose between the multi-plex test (ODxTT) or single-plex test in routine diagnostics.

DOI： 10.1016/j.ctarc.2022.100614

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.3769/radioisotopes.71.135

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/jhbp.1101

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Publishing type：Research paper (scientific journal)   Publisher：Anticancer Research USA Inc.  

Background/Aim: Pulmonary enteric adeno­carcinoma (PEAC) is a rare type of non-small cell lung cancer (NSCLC), for which no established standard treatment exists. Combination therapy with the anti-programmed cell death protein 1 antibody pembrolizumab and platinum-containing chemotherapy is the standard treatment for NSCLC patients, but its effectiveness in PEAC is uncertain. Case Report: We present a 68-year-old man with chemotherapy-naïve advanced PEAC who responded to a combination of pembrolizumab and platinum-containing chemotherapy. Conclusion: The number of PEAC cases is small, and no clinical trials have been conducted to determine an optimal chemotherapy regimen. In this case, we showed that pembrolizumab combined with platinum-containing chemotherapy might effectively treat PEAC.

DOI： 10.21873/cdp.10102

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Language：English  

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DOI： 10.1111/resp.14186

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Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

<sec><title>Background:</title> 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.

</sec><sec><title>Methods:</title> 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.

</sec><sec><title>Results:</title> 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 &lt; 0.001), and serious AE (N1I3 61.4%, N3I1 47.8%, p = 0.004).

</sec><sec><title>Conclusions:</title> 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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DOI： 10.1177/17588359211058393

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Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/17588359211058393

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Pembrolizumab alone or in combination with chemotherapy is a standard treatment for patients with non-small-cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression. However, no study has compared the efficacies of these two regimens. Therefore, we aimed to compare the efficacy of pembrolizumab alone and in combination with chemotherapy in NSCLC patients with high PD-L1 expression. METHODS: We conducted a multicenter retrospective trial involving patients with diagnosed unresectable or recurrent NSCLCs who had received pembrolizumab with or without chemotherapy in the first-line setting. Patients were divided into monotherapy and combination therapy groups. The progression-free survival (PFS), overall survival (OS), and response rate (RR) were analyzed and compared between the groups. Clinical characteristics of patients were analyzed to assess their possible relationship with treatment outcomes. RESULTS: We enrolled 96 patients from five hospitals. Of these, 47 and 49 patients received monotherapy and combination therapy, respectively. The median PFS was 343 and 328 days in the monotherapy and combination therapy groups, respectively (hazard ratio 1.003, p = 0.99). No statistically significant differences were observed in the OS and RR between the two groups. However, in patients with metastases to the liver, lung, adrenal glands, bone, or lymph nodes, the PFS was longer in the monotherapy group than in the combination therapy group. CONCLUSION: Although the PFS, OS, and RR were not significantly different between patients treated with pembrolizumab alone and or with pembrolizumab in combination with chemotherapy, patients with NSCLC having metastases to specific sites may benefit more from monotherapy.

DOI： 10.1111/1759-7714.14252

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1111/1759-7714.14229

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1177/17588359211065152

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Language：English  

A 70-year-old man diagnosed with idiopathic pulmonary fibrosis (IPF) one year earlier developed progressive exertional dyspnea 3 weeks after onset of coronavirus disease 2019 (COVID-19). High-resolution computed tomography showed new extensive ground-glass opacities with rapidly progressive honeycombing. Although he was diagnosed with acute exacerbation (AE) of IPF triggered by COVID-19 and received methylprednisolone pulse therapy twice within one month, there was no improvement of oxygenation and lung involvement. Three months after COVID-19 onset, it was decided to provide best supportive care. An AE of IPF as a sequela of COVID-19, which is recognized as macrophage activation syndrome, is fatal, and in this case, the measurement of serum heme oxygenase-1, which is a macrophage activation biomarker involved in pulmonary cellular protection against oxidative stress, was useful for tracking disease activity.

DOI： 10.1016/j.rmcr.2022.101615

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Language：English   Publishing type：Research paper (scientific journal)  

Lung lesions of Hodgkin's lymphoma (HL) are rare and difficult to diagnose by nonsurgical biopsy. We herein present the case of a 72-year-old Japanese male who presented with accumulation of lung infiltrates and masses bilaterally on the lungs for 3 years. Although transbronchial lung biopsy (TBB) and computed tomography-guided biopsy were conducted several times, his diagnosis remained inconclusive. On further deterioration of lung lesions, the patient was transferred to our hospital. Positron emission tomography revealed increased accumulation in the bilateral lungs and right supraclavicular lymph nodes. Surgical biopsy of the lymph node was performed. He was finally diagnosed with HL and underwent chemotherapy with doxorubicin, vinblastine, dacarbazine, and brentuximab vedotin. After chemotherapy, the lung lesion showed significant regression. A literature review indicated that the diagnostic success rate of TBB was low (18.5%) in cases of lung lesions in HL.

DOI： 10.1111/1759-7714.14190

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/cid/ciab922

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The incidence and risk factors of severe anaphylaxis by intravenous anti-cancer drugs are unclear, whereas those of milder reactions have been reported. STUDY DESIGN: Electronic medical charts of cancer patients who have undergone intravenous chemotherapy between January 2013 and October 2020 in a university hospital were retrospectively reviewed. Non-epithelial malignancies were also included in the analysis. "Severe anaphylaxis" was judged using Brown's criteria: typical presentation of anaphylaxis and one or more of hypoxia, shock, and neurologic compromise. (UMIN000042887). RESULTS: Among 5584 patients (2964 males [53.1%], 2620 females [46.9%], median age 66 years), 88,200 person-day anti-cancer drug administrations were performed intravenously, and 27 severe anaphylaxes were observed. The causative drugs included carboplatin (14 cases), paclitaxel (9 cases), and cisplatin, docetaxel, trastuzumab, and cetuximab (1 case each). The person-based lifetime incidence of severe anaphylaxis for patients who received at least one intravenous chemotherapy was 0.48% (27/5584, 95% confidence interval (CI) 0.30%-0.67%) and the administration-based incidence was 0.031% (27/88,200, 95% CI 0.019%-0.043%). Among 124 patients who received at least 10 carboplatin administrations, 10 patients experienced carboplatin-induced severe anaphylaxis (10/124, 8.1%, 95% CI 3.0%-13.1%). Carboplatin caused severe anaphylaxis after at least 9-min interval since the drip started. Thirteen out of 14 patients experienced carboplatin-induced severe anaphylaxis within a 75-day interval from the previous treatment. Paclitaxel infusion caused severe anaphylaxis after a median of 5 min after the first drip of the day at a life-long incidence of 0.93% (9/968, 95% CI 0.27%-1.59%). CONCLUSION: We elucidated the high-risk settings of chemotherapy-induced severe anaphylaxis.

DOI： 10.1002/cam4.4252

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BACKGROUNDS: Recent studies have reported increased risks of adverse events from systemic corticosteroids even with only low-dose or short-term use. Some patients with asthma experience complications requiring systemic corticosteroids. However, few studies have examined issues associated with administration of systemic corticosteroids for reasons other than asthma among subjects with asthma. OBJECTIVES: We investigated patterns of systemic corticosteroid exposure for reasons other than asthma in subjects with asthma. METHOD: We retrospectively reviewed the records of adult subjects with asthma followed up for >1 year at Yokohama City University Hospital from January 1, 2010, to December 31, 2019. We investigated patterns and reasons for systemic corticosteroid use during follow-up. In addition, factors related to systemic corticosteroid use for reasons likely other than asthma were investigated. RESULTS: Among the 568 subjects with asthma analyzed, 326 (57.4%) had received systemic corticosteroids for some reason. Among those 326 patients, 120 (36.8%) had received systemic corticosteroids for reasons likely other than asthma. Multivariable analysis revealed rheumatoid arthritis, eosinophilic granulomatosis with polyangiitis, other collagen vascular diseases, chronic rhinosinusitis, and malignancy as positively associated with systemic corticosteroid exposure for reasons likely other than asthma in subjects with asthma. CONCLUSIONS: About 40% of systemic corticosteroid use in subjects with asthma was for reasons likely other than asthma. Clinicians should be aware of their asthma patients' exposures to systemic corticosteroids for nonasthma reasons, to avoid missing adverse events or underestimating the severity of asthma, and to reduce systemic corticosteroid use.

DOI： 10.1159/000518461

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PURPOSE: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA0-Tyr3-octreotate (177Lu-DOTATATE) is one of the most reliable treatments for unresectable, progressive neuroendocrine tumors (NETs) with somatostatin receptor expression. We have, for the first time, reported the results of the tolerability, safety, pharmacokinetics, dosimetry, and efficacy of this treatment for Japanese patients with NET. METHODS: Patients with unresectable, somatostatin receptor scintigraphy (SRS)-positive NETs were enrolled in this phase I clinical trial. They were treated with 29.6 GBq of 177Lu-DOTATATE (four doses of 7.4 GBq) combined with amino acid solution infusion plus octreotide long-acting release (LAR) 30 mg. The primary objective of this study was to evaluate the tolerability, safety, pharmacokinetics, and dosimetry of a single administration of this treatment in patients with SRS-positive NETs. RESULTS: Six Japanese patients (three men and three women; mean age 61.5 years; range 50-70 years) with SRS-positive unresectable NETs were recruited. 177Lu-DOTATATE was eliminated from the blood in a two-phase manner. Cumulative urinary excretion of radioactivity was 60.1% (range 49.0%-69.8%) within the initial 6 h. The cumulative renal absorbed dose for 29.6 GBq of 177Lu-DOTATATE was 16.8 Gy (range 12.0-21.2 Gy), and the biological effective dose was 17.0 Gy (range 12.2-21.5 Gy). Administration of 177Lu-DOTATATE was well tolerated, with no dose-limiting toxicities. Grade 3 lymphopenia occurred in two (33.3%) cases, but there were no other severe toxicities. Four patients achieved partial response (objective response rate, 66.7%), one patient had stable disease, and one patient had progressive disease. CONCLUSION: PRRT with 177Lu-DOTATATE was well-tolerated and showed good outcomes in Japanese patients with unresectable NETs. Peptide receptor radionuclide therapy, 177Lu-DOTA0-Tyr3-octreotate .

DOI： 10.1007/s12149-021-01674-9

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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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%.

DOI： 10.21037/tlcr-21-419

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Language：Japanese   Publishing type：Research paper (scientific journal)  

After the identification of the new coronavirus disease(COVID-19)in December 2019, it has spread rapidly around the world. The COVID-19 pandemic has forced medical systems to limit their services, promote telehealth, prolong visits to clinics, and postpone scheduled surgical operations. The mortality rate of COVID-19 in patients with lung cancer appears to be significantly higher than that of patients with other cancers. Medical care offered to patients with lung cancer should take into account the risk of COVID-19 associated with visits to clinics and treatments. This review outlines the efforts of lung cancer oncologists in the"With COVID-19"era based on the current evidence and statements from domestic and foreign academic societies and organizations.

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Risk factors associated with mortality in invasive pneumococcal disease remain unclear. The present work is a meta-analysis of studies that enrolled only patients with invasive pneumococcal disease and reported on mortality. Potentially eligible reports were identified from PubMed, CHAHL, and Web of Science, comprising 26 reports in total. Overall mortality for invasive pneumococcal disease was reported as 20.8% (95% confidence interval (CI) 17.5-24%). Factors associated with mortality were age (odds ratio (OR) 3.04, 95% CI 2.5-3.68), nursing home (OR 1.62, 95% CI 1.13-2.32), nosocomial infection (OR 2.10, 95% CI 1.52-2.89), septic shock (OR 13.35, 95% CI 4.54-39.31), underlying chronic diseases (OR 2.34, 95% CI 1.78-3.09), solid organ tumor (OR 5.34, 95% CI 2.07-13.74), immunosuppressed status (OR 1.67, 95% CI 1.31-2.14), and alcohol abuse (OR 3.14, 95% CI 2.13-4.64). Mortality rates with invasive pneumococcal disease remained high, and these findings may help clinicians provide appropriate initial treatment for this disease.

DOI： 10.1038/s41598-021-91234-y

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ABSTRACT: The Coronavirus disease 2019 pandemic continues to spread worldwide. Because of the absence of reliable rapid diagnostic systems, patients with symptoms of Coronavirus disease 2019 are treated as suspected of the disease. Use of computed tomography findings in Coronavirus disease 2019 are expected to be a reasonable method for triaging patients, and computed tomography-first triage strategies have been proposed. However, clinical evaluation of a computed tomography-first triage protocol is lacking.The aim of this study is to investigate the real-world efficacy and limitations of a computed tomography-first triage strategy in patients with suspected Coronavirus disease 2019.This was a single-center cohort study evaluating outpatients with fever who received medical examination at Yokohama City University Hospital, prospectively registered between 9 February and 5 May 2020. We treated according to the computed tomography-first triage protocol. The primary outcome was efficacy of the computed tomography-first triage protocol for patients with fever in an outpatient clinic. Efficacy of the computed tomography-first triage protocol for outpatients with fever was evaluated using sensitivity, specificity, positive predictive value, and negative predictive value. We conducted additional analyses of the isolation time of feverish outpatients and final diagnoses.In total, 108 consecutive outpatients with fever were examined at our hospital. Using the computed tomography-first triage protocol, 48 (44.9%) patients were classified as suspected Coronavirus disease 2019. Nine patients (18.8%) in this group were positive for severe acute respiratory syndrome coronavirus 2 using polymerase chain reaction; no patients in the group considered less likely to have Coronavirus disease 2019 tested positive for the virus. The protocol significantly shortened the duration of isolation for the not-suspected versus the suspected group (70.5 vs 1037.0 minutes, P < .001).Our computed tomography-first triage protocol was acceptable for screening patients with suspected Coronavirus disease 2019. This protocol will be helpful for appropriate triage, especially in areas where polymerase chain reaction is inadequate.

DOI： 10.1097/MD.0000000000026161

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Language：Japanese   Publisher：(一社)日本呼吸器内視鏡学会  

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BACKGROUND: Immune checkpoint inhibitors are a standard treatment for advanced lung cancer, although it remains important to identify biomarkers that can accurately predict treatment response. Immune checkpoint inhibitors enhance the antitumor T-cell response, and interferon-γ plays an important role in this process. Therefore, this study evaluated whether the number of interferon-γ-releasing peripheral T cells after phytohemagglutinin stimulation in the interferon-γ release assay might act as a biomarker for the response of non-small cell lung cancer to immune checkpoint inhibitor treatment. METHODS: Data were retrospectively collected regarding 74 patients with non-small cell lung cancer who had received immune checkpoint inhibitors. Pretreatment screening tests had been performed using the T-SPOT.TB assay, which quantifies the number of interferon-γ-releasing T cells (as immunospots) in response to phytohemagglutinin and tuberculosis-specific antigen stimulation. Clinical factors and the number of spots in the T-SPOT fields were evaluated for associations with patient outcomes. The median number of spots was used to categorize patients as having high or low values, and the two groups were compared. RESULTS: Relative to patients with a low ratio, patients with a high ratio of phytohemagglutinin/tuberculosis-specific antigen spots (i.e. more responsive T cells) had significantly better progression-free survival after immune checkpoint inhibitor treatment. When we only considered patients with negative T-SPOT results, a high number of phytohemagglutinin-stimulated spots corresponded to significantly longer progression-free survival. CONCLUSION: The T-SPOT.TB assay can be used to quantify the number of immunospots in response to antigen stimulation, which may predict the response to immune checkpoint inhibitors in patients with non-small cell lung cancer.

DOI： 10.1111/1759-7714.13978

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Language：Japanese   Publishing type：Research paper (scientific journal)  

An 86‒year‒old man with chronic kidney disease underwent surgical resection for combined large‒cell neuroendocrine carcinoma of the left lower lobe of the lung(pT2aN1M0, stage ⅡB). Five months later, multiple liver and bone metastases and mediastinal lymph node recurrence were detected. After 9 courses of amrubicin monotherapy(32 mg/m2 for 3 consecutive days), his tumor marker levels normalized, and radiological examination revealed a complete tumor response. Adverse events occurred, but they were tolerable except a decrease in the neutrophil count. The patient remained in good condition for several months but died of tumor relapse 22 months after the initial recurrence. Amrubicin monotherapy was considered to be one of the treatment choices for recurrent large‒cell neuroendocrine carcinoma of the lung in elderly patients.

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Although objective response rate and disease control rate are commonly used as primary endpoints of lung cancer trials, it remains unclear whether objective response rate and disease control rate correctly reflect the overall survival in a non-small cell lung cancer phase II trial evaluating a non-first-line chemotherapy. Objective response rate might be easily affected by chance because the small number of patients in each trial achieved complete or partial response in the phase II non-first-line setting. This study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (UMIN000040412). Four databases were searched for eligible trials. A Spearman's rank correlation with hazard ratio of overall survival was calculated each for odds ratio of objective response rate, difference of objective response rate (%), odds ratio of disease control rate, and difference of disease control rate (%). Of 74 eligible trials, 73 reported objective response rate and 68 reported disease control rates. Nine (12%) trials included patients with driver mutation status. Thirteen (18%) and two (3%) RCTs specifically included adenocarcinoma/non-squamous and squamous subtype of non-small cell lung cancer, respectively. The Eastern Cooperative Oncology Group performance status 0-2 (N=41, 55%) and the performance status 0-1 (N=25, 34%) were frequently used performance status criteria. The median number of patients in the two arms was 116 (interquartile range, 82-159). The correlation between trial-level odds ratio of objective response rate and hazard ratio of overall survival was weak (r=-0.29, 95% CI: -0.49 to -0.05, P=0.014). An exploratory subgroup analysis suggested that fewer responders were associated with poorer correlation. Odds ratio of disease control survival (r=-0.53, 95% CI: -0.68 to -0.32, P<0.001) had moderate rank correlations with hazard ratio of overall survival. Instead of objective response rate, disease control rate should be used as the primary endpoint in a randomized phase II trial evaluating non-first-line chemotherapy for non-small cell lung cancer.

DOI： 10.21037/tlcr-20-1120

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PURPOSE: Guidelines and systematic reviews frequently warn of inhaled corticosteroid (ICS)-induced glaucoma. However, most of the published studies deny it. METHODS: We performed a systematic review of randomized, cohort, nested-case control, cross-sectional studies by using Meta-analyses of Observational Studies in Epidemiology statement. Four major databases, PubMed, EMBASE, Cochrane Search Manager, and the Web of Science Core Collection as well as meta-analysis were used. Studies comparing incidence, prevalence and intraocular pressure (IOP) between patients who were treated with and without ICSs were included. A random-model meta-analysis was performed using the inverse variance method. RESULTS: Out of 623 studies screened, 18 with 31,665 subjects were finally included. No significant difference between the 2 groups was observed for crude glaucoma incidence (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.86-1.04; P = 0.26; I² = 0%; P for heterogeneity = 0.57) as a primary endpoint, adjusted glaucoma incidence (OR, 0.90; 95% CI, 0.65-1.24; P = 0.64), crude prevalence (OR, 1.82; 95% CI, 0.23-14.19; P = 0.57), adjusted prevalence (OR, 1.22; 95% CI, 0.50-2.96; P = 0.66), IOP change during ICS treatment (mean difference [MD] +0.01 mmHg; 95% CI, -0.19-0.20; P = 0.95), and single measurement IOP (MD +0.37 mmHg; 95% CI, -0.24-0.97; P = 0.23). Time-to-event analysis for glaucoma development as one of the secondary endpoints (adjusted hazard ratio, 0.52; 95% CI, 0.28-0.96) suggested a reverse association between ICS and glaucoma. CONCLUSIONS: The ophthalmological side effects of ICSs, such as glaucoma and intraocular hypertension, should not be exaggerated. TRIAL REGISTRATION: University Hospital Medical Information Network Center Clinical Trial Registry Identifier: UMIN000040351.

DOI： 10.4168/aair.2021.13.3.435

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

BACKGROUND: Differences in the resistance mechanisms of epidermal growth factor receptor tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor mutations are unknown. This meta-analysis aimed to clarify the differences in resistance mechanisms after treatment with various epidermal growth factor receptor tyrosine kinase inhibitors. METHODS: We systematically searched PubMed, Cochrane, and Web of Science on July 29, 2020, for relevant studies on acquired resistance mechanisms against epidermal growth factor receptor tyrosine kinase inhibitors. The primary outcome measure was differences in the resistance mechanism between individual or generations of epidermal growth factor receptor tyrosine kinase inhibitors. RESULTS: In total, 33 trials involving 2418 individuals were included and analyzed. T790M was significantly less frequent after afatinib treatment (40.2%, 95% confidence interval [CI]: 31.7%-48.7%) than after gefitinib and erlotinib treatments (52.5%, 95% CI: 48.7%-56.3%, p = 0.005). There were no significant differences between Asian and non-Asian patients in the incidence of T790M after gefitinib, erlotinib, and afatinib treatments. Regarding epidermal growth factor receptor pathway-independent resistant mechanisms, the incidences of small cell lung cancer transformation (osimertinib: 7.9%, 95% CI: 3.6%-12.2%, others: 2.3%, 95% CI: 0.8%-3.8%) and Kirsten rat sarcoma (KRAS) viral oncogene homolog mutation (osimertinib: 4.6%, 95% CI: 1.5%-7.7%, others: 0.2%, 95% CI: 0.0%-1.7%) were significantly higher following osimertinib treatment than with others. CONCLUSIONS: Significant differences in the incidence of resistance mechanisms among epidermal growth factor receptor tyrosine kinase inhibitors exist, which should be taken into consideration when choosing the treatment strategy.

DOI： 10.1111/1759-7714.13878

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：横浜市立大学医学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

BACKGROUND: Despite numerous studies on ABO blood group and risk of tuberculosis, no consensus has been reached. METHODS: We conducted a systematic review following the Meta-Analysis of Observational Studies in Epidemiology group statement. English language articles providing odds ratio data regarding tuberculosis risk among ABO groups were eligible. Least-squares approach random-model network and random-model pairwise meta-analyses were conducted. The protocol-specified primary outcome was tuberculosis risk among ABO groups in the form of odds ratios calculated via a network meta-analysis. RESULTS: We identified 28 studies with 30 populations comprising 15,664 patients with tuberculosis and 254,610 controls. Subjects with AB blood type had a higher risk of becoming infected with tuberculosis than those with blood type O (odds ratio (OR) = 1.26, 95% confidence interval (CI): 1.14-1.38), A (OR = 1.25, 95% CI: 1.14-1.38), and B (OR = 1.22, 95% CI: 1.11-1.34). Pairwise comparison revealed that AB blood type was a risk factor for tuberculosis with OR = 1.23 (95% CI: 1.02-1.48) compared to other blood types. Region-based subgroup analyses suggested that the AB blood group was a substantial risk in Africa (OR = 1.78, 95% CI: 1.39-2.28) and India (OR = 1.48, 95% CI: 1.14-1.92). CONCLUSIONS: AB blood group is a risk factor for tuberculosis of a substantial magnitude in Africa and India.

DOI： 10.1016/j.ijid.2021.01.057

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Language：Japanese   Publisher：(一社)日本呼吸器内視鏡学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J00298&link_issn=&doc_id=20210413250006&doc_link_id=%2Fcf0brond%2F2021%2F004302%2F007%2F0112-0116%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcf0brond%2F2021%2F004302%2F007%2F0112-0116%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Carboplatin plus pemetrexed followed by maintenance pemetrexed is expected to be well-tolerated by the elderly. This multicenter, prospective study examined the efficacy and tolerability of the regimen in elderly patients with previously untreated advanced non-squamous non-small cell lung cancer. METHODS: The primary endpoint was the 1-year survival rate, with secondary endpoints of response rate (RR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse event rate. Efficacy was compared between patients with performance status (PS) 0 and 1. RESULTS: Forty-one patients were enrolled between March 2011 and April 2016. Median age was 76.0 years. The 1-year survival rate was 73% (95% confidence interval (CI), 56-84%). RR was 44%, DCR was 81%, median PFS was 7.2 months (95%CI, 3.98-9.20 months), and median OS was 17.4 months (95%CI, 13.60-22.83 months). Twenty-one patients (51%) transitioned to maintenance therapy. Toxicities of grade ≥ 3 during the induction phase included anemia (37%), thrombocytopenia (29%), neutropenia (22%), appetite loss (15%), nausea (10%), bacterial pneumonia (7%), febrile neutropenia (5%), and interstitial pneumonia (2%). Treatment was discontinued in two patients with interstitial pneumonia, but no deaths were encountered. During the maintenance phase, one patient needed dose reductions due to phlegmon. No significant difference in efficacy was seen between PS 0 and PS 1. CONCLUSION: Carboplatin and pemetrexed followed by maintenance pemetrexed for non-squamous non-small cell lung cancer in elderly patients appear effective and tolerable.

DOI： 10.1111/ajco.13488

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Language：Japanese   Publisher：日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会  

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Language：Japanese   Publisher：日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会  

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DOI： 10.1097/MJT.0000000000001321

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Background: Although the US government approved hydroxychloroquine (HCQ) and chloroquine (CQ) for hospitalized coronavirus disease 19 (COVID-19) patients, some studies denied efficacy of HCQ and CQ. We aimed to evaluate HCQ/CQ treatment for COVID-19. Methods: Five databases were searched on April 15, 2020, without publication date restriction. We followed both Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology statement reporting recommendations. A random-model meta-analysis was conducted to pool odds ratio (OR) and hazard ratio (HR). The quality of evidence for each outcome and the final recommendation was assessed using the GRADE guidelines of the American College of Chest Physicians. Results: We identified four randomized controlled trials (RCTs) and four observational studies with 2,063 COVID-19 cases. All-cause mortality was not affected by the administration of HCQ/CQ [OR: 1.05, 95% confidence interval (CI): 0.53-2.09, P=0.89]. No improvement of viral clearance was found neither by time-to-event analysis (HR: 1.19, 95% CI: 0.74-1.94, P=0.47) nor frequency on day 7 (OR: 1.47, 95% CI: 0.33-6.63, P=0.62). HCQ/CQ treatment increased the risk of the any adverse event with OR of 3.56 (95% CI: 1.62-7.83, P=0.002). Conclusions: HCQ/CQ failed to decrease the all-cause mortality (very low quality evidence) and did not improve viral clearance (low or very low quality evidence) but increased the risk of any adverse event (moderate quality evidence). Routine administration of HCQ/CQ for COVID-19 patients is not recommended (weak recommendation, Grade 2C).

DOI： 10.21037/jtd-20-2022

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Background: Pneumonia is a common disease among the aging population in Japan. Hence, it is important to elucidate the risks related to pneumonia mortality. Since Streptococcus pneumoniae is the most commonly observed pathogen, pneumococcal vaccination is recommended to older adults. Therefore, this study aimed to clarify the clinical features of pneumonia, including the status of pneumococcal vaccination, in hospitalized older adult patients in Japan. Methods: This single-centered retrospective study was conducted by reviewing the medical records of all patients with acute pneumonia at Fujisawa City Hospital in Japan from April 2018 to March 2019. Patients were divided into two groups based on their history of pneumococcal vaccination. The primary endpoint was in-hospital mortality, while the secondary endpoint was risk factors associated with mortality. Results: We included 93 patients with pneumonia in this retrospective study. Although the mortality rate was higher in the vaccinated group (15.8%) than in the unvaccinated group (9.1%), vaccination status was not identified as a significant risk factor for mortality after multivariable logistic regression (odds ratio: 2.71; 95% confidence interval: 0.667-11.02; p=0.16). In addition, the A-DROP score was identified as an independent risk factor (odds ratio: 2.64; 95% confidence interval: 1.22-5.72; p=0.008). Conclusions: Our study suggested that the A-DROP score is a risk factor of mortality for pneumonia in older adults. In addition, pneumococcal vaccination history was related to increased mortality; however, the influence of the vaccination remains unclear because of the small sample size.

DOI： 10.1155/2021/5644824

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Background: Serum Krebs von den Lungen-6 (KL-6) measurement is widely used to assess disease activity or prognosis in patients with interstitial lung diseases (ILDs). However, the clinical differences between high and low serum KL-6 levels at the time of acute exacerbation (AE) of ILD are not well known. Methods: Clinical parameters including age, sex, Charlson Comorbidity Index score (CCIS), blood biomarkers, high-resolution CT findings, and disease mortality were retrospectively compared between high and low KL-6 (cutoff value: 1000 U/mL) patients at the time of diagnosis of AE of ILDs. Results: Thirty-eight high serum KL-6 and 57 low serum KL-6 patients were included. There was no significant difference in 6-month mortality between them (P = 0.685), whereas serum lactate dehydrogenase was a significant predictor of 6-month mortality in the high serum KL-6 patients (odds ratio (OR): 1.006; 95% confidence interval (CI): 1.003-1.009; P < 0.001), and CCIS (OR: 1.502; 95% CI: 1.242-1.838; P < 0.001) and sex (OR: 5.751; 95% CI: 1.121-105.163; P = 0.033) were significant predictors in low serum KL-6 patients. In addition, the incidences of congestive heart failure, symptomatic chronic pulmonary disease, cerebrovascular disease, and second metastatic solid tumours were significantly higher in nonsurvivors with low serum KL-6 than in other groups (P < 0.05). Conclusions: The clinical features in patients with AEs of ILDs may differ depending on the serum KL-6 level, and clinicopathological examination according to this subtyping guided by the serum KL-6 level is essential.

DOI： 10.1155/2021/9099802

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Background: The purpose of this retrospective study was to clarify whether the presence of honeycombing on computed tomography (CT) can affect the prognosis of patients with acute exacerbations (AEs) of interstitial lung diseases (ILDs). Methods: Clinical parameters including age, sex, Charlson Comorbidity Index Score (CCIS), blood biomarkers, and 3-month mortality were retrospectively compared between the CT honeycombing present and absent groups at the diagnosis of AEs of ILDs. Results: Ninety-five patients who were on corticosteroid pulse therapy were assessed. Though log-rank tests showed that Kaplan-Meier survival curves of the high and low ground-glass opacity (GGO) score groups differed significantly in 3-month mortality in patients with AEs of idiopathic ILDs (P = 0.007) and overall patients (P = 0.045), there was no significant difference between the CT honeycombing present and absent groups in patients with AEs of idiopathic ILDs (P = 0.472) and AEs of secondary ILDs (P = 0.905), as well as of overall patients (P = 0.600). In addition, whereas CCIS (OR, 1.436; 95% CI, 1.156-1.842; P < 0.001) was a significant predictor of 3-month mortality in the CT honeycombing absent group, serum LDH (OR, 1.005; 95% CI, 1.002-1.007; P = 0.001) was a significant predictor in the CT honeycombing present group. Conclusions: The clinical features of patients with or without honeycombing may differ due to the difference in prognostic factors, but these groups were found to have similar prognoses 3 months after AE onset, and clinicopathological examinations according to these groups are essential.

DOI： 10.1155/2021/7456315

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Publishing type：Research paper (scientific journal)   Publisher：Sociedade Brasileira de Pneumologia e Tisiologia  

DOI： 10.36416/1806-3756/e20200520

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

<title>Abstract</title><sec>
<title>Background</title>
Oxidative stress plays an important role in acute lung injury, which is associated with the development and progression of acute respiratory failure. Here, we investigated whether the degree of oxidative stress as indicated by serum heme oxygenase-1 (HO-1) is clinically useful for predicting prognosis among the patients with acute respiratory distress syndrome (ARDS) and acute exacerbation of interstitial lung disease (AE-ILD).


</sec><sec>
<title>Methods</title>
Serum HO-1 levels of newly diagnosed or untreated ARDS and AE-ILD patients were measured at diagnosis. Relationships between serum HO-1 and other clinical parameters and 1 and 3-month mortality were evaluated.


</sec><sec>
<title>Results</title>
Fifty-five patients including 22 of ARDS and 33 of AE-ILD were assessed. Serum HO-1 level at diagnosis was significantly higher in ARDS patients than AE-ILD patients (87.8 ± 60.0 ng/mL vs. 52.5 ± 36.3 ng/mL, <italic>P</italic> &lt;  0.001). Serum HO-1 correlated with serum total bilirubin (R = 0.454, P &lt;  0.001) and serum LDH (R = 0.500, P &lt;  0.001). In both patients with ARDS and AE-ILDs, serum HO-1 level tended to decrease from diagnosis to 2 weeks after diagnosis, however, did not normalized. Composite parameters including serum HO-1, age, sex, and partial pressure of oxygen in arterial blood/fraction of inspired oxygen (P/F) ratio for prediction of 3-month mortality showed a higher AUC (ARDS: 0.925, AE-ILDs: 0.892) than did AUCs of a single predictor or combination of two or three predictors.


</sec><sec>
<title>Conclusion</title>
Oxidative stress assessed by serum HO-1 is persistently high among enrolled patients for 2 weeks after diagnosis. Also, serum HO-1 levels at the diagnosis combined with age, sex, and P/F ratio could be clinically useful for predicting 3-month mortality in both ARDS and AE-ILD patients.


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DOI： 10.1186/s12890-020-01341-1

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Other Link： http://link.springer.com/article/10.1186/s12890-020-01341-1/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

Data from China have shown that the ratio of Mycobacterium tuberculosis-specific antigen (TBAg) spots obtained from the T-SPOT.TB test to the number of positive control phytohemagglutinin (PHA) spots (TBAg/PHA ratio) could help distinguish between active tuberculosis infection (ATBI) and latent tuberculosis infection (LTBI). As the applicability of the T-SPOT.TB test may differ according to region and race, we retrospectively verified the utility of the TBAg/PHA ratio in distinguishing between ATBI and LTBI in Japan. The TBAg/PHA ratio was significantly lower in the LTBI group than in the ATBI group. Area under the receiver operating characteristic curve (AUC) analysis between ATBI and LTBI according to the TBAg/PHA ratio was 0.76, with a sensitivity of 65.8% and a specificity of 75.6%. The best AUC was obtained when the TBAg/PHA ratio was divided by both lymphocyte count and albumin levels. Our results demonstrate that, in Japan, the TBAg/PHA ratio is superior to TBAg alone for distinguishing between ATBI and LTBI. In addition, the sensitivity and specificity were improved by combining the TBAg/PHA ratio with lymphocyte count and albumin levels.

DOI： 10.1016/j.tube.2020.101992

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

A 77-year-old man who had a persistent productive cough for one month was admitted to our hospital. Chest computed tomography (CT) revealed subpleural nodular opacities, irregular pleural thickening with bilateral basal predominance, and a small right pleural effusion. Aspirated fluid was exudative and had the appearance of chylothorax without malignant cells. Surgical lung biopsy specimen showed focal proliferation of neoplastic epithelial cells with lepidic-predominant pattern and abundant mucus in the alveolar spaces, consistent with invasive mucinous adenocarcinoma (IMA). The results of PD-L1 expression and the EGFR, ALK, ROS1, and BRAF mutation status analyzed by next generation sequencer were all negative. IMA should be considered in the differential diagnosis of subpleural micronodular opacities accompanied by pleural effusion (chylothorax) on chest CT. KEY POINTS: Significant findings of the study This case showed subpleural micronodular opacities and chylothorax as unusual chest computed tomography (CT) patterns for invasive mucinous adenocarcinoma (IMA). What this study adds Invasive mucinous adenocarcinoma (IMA) should be considered in the differential diagnosis of subpleural micronodular opacities accompanied by pleural effusion on chest CT.

DOI： 10.1111/1759-7714.13665

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1759-7714.13665

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

BACKGROUND: Advanced non-small cell lung cancer (NSCLC) has a high mortality rate and poor prognosis. However, outcomes have gradually improved after the introduction of novel immunotherapies, including immune checkpoint inhibitors (ICIs). Although programmed death-ligand 1 (PD-L1) expression in tumor tissues is a known biomarker for guiding ICI treatment of NSCLC, challenges such as difficulty of liquid biopsy and heterogeneous results during treatment persist. This study evaluated the potential of miR200b as a surrogate biomarker for PD-L1 expression. METHODS: We used the human lung cancer cell lines H226, H460, H520, A549, and H1975. miR200b expression in blood and bronchoscopy specimens of NSCLC patients was evaluated using reverse-transcription-quantitative PCR. Using flow cytometry, PD-L1 expression in vitro, as well as in tumor tissues, was evaluated after transfection with a mimic miR200b or siRNA. RESULTS: miR200b expression negatively correlated with PD-L1 expression in all cell lines. The induction or knockdown of miR200b also altered PD-L1 expression in vitro. The patient group with a PD-L1 tumor proportion score ≥ 50% had significantly lower miR200b expression in the bronchoscopy specimens (P = 0.025) and serum-derived exosomes (P = 0.022) than that with PD-L1 tumor proportion score < 50%. CONCLUSIONS: miR200b can regulate PD-L1 expression in lung cancer cells, and miR200b expression in clinical specimens negatively correlated with PD-L1 expression. Thus, miR200b may be a useful surrogate biomarker for PD-L1 expression in lung cancer patients. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: High PD-L1 expression was linked to low miR200b expression, whereas low PD-L1 expression was linked to high miR200b expression in human lung cancer patients. Thus, miR200b overexpression or silencing can control PD-L1 expression in cancer cells. What this study adds We demonstrated the potential of miR200b as a surrogate biomarker for PD-L1 expression in lung cancer patients.

DOI： 10.1111/1759-7714.13653

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1759-7714.13653

Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AME Publishing Company  

Background: Prognostic factors have yet to be established for patients with interstitial lung disease (ILD). We aimed to clarify whether the Charlson Comorbidity Index score (CCIS) could help predict disease prognosis in patients with ILD. Methods: Among ILD patients treated between April 2013 and April 2017, we retrospectively assessed the relationship between baseline clinical parameters including age, sex, CCIS, ILD diagnosis, pulmonary function test results, and 3-year ILD-related events including cause-specific death and first acute exacerbation (AE). Results: We assessed 180 patients (mean age, 74 years), all of whom underwent pulmonary function testing including percentage predicted diffusion capacity for carbon monoxide (%DLco). Underlying pathologies included idiopathic pulmonary fibrosis (IPF) in 57 cases, idiopathic nonspecific interstitial pneumonia (iNSIP) and collagen vascular disease-related interstitial pneumonia in 117 cases, and chronic hypersensitivity pneumonia (CHP) in 6 cases. A composite scoring system comprising IPF diagnosis, CCIS, and %DLco provided a favorable C-index (0.825) for predicting 3-year ILD-related events. The nomogram for 3-year prognosis revealed the largest contributions from CCIS, %DLco and IPF diagnosis. Conclusions: This composite scoring system accounting for IPF diagnosis, CCIS, and %DLco could provide a useful tool for predicting prognosis in relatively mild ILD patients tolerated to pulmonary diffusion capacity testing.

DOI： 10.21037/jtd-20-1302

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Language：Japanese   Publisher：日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会  

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Language：Japanese   Publisher：日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会  

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Language：Japanese   Publisher：日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会  

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Language：Japanese   Publisher：(一社)日本結核・非結核性抗酸菌症学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

INTRODUCTION: As most patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) develop progressive disease after treatment with osimertinib, it is important to develop more effective treatment options. Afatinib has been shown to be more effective in in vitro studies than osimertinib when used in cancer cell lines containing some specific EGFR mutations. Therefore, afatinib may be an effective solution, especially when used in combination with an anti-VEGF agent such as bevacizumab. METHODS: A phase II multicenter, open-label, single-arm trial has been initiated to evaluate the efficacy and safety of afatinib and bevacizumab combination as salvage therapy for EGFR-mutated lung cancer in patients previously treated with osimertinib. The primary endpoint will be the objective response rate (ORR) and secondary endpoints are progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs). DISCUSSION: A previous study indicated that afatinib inhibits lung cancer cells with specific EGFR mutations more effectively than other EGFR-TKIs such as osimertinib. Therefore, we expect that combination therapy using afatinib and bevacizumab will be effective in patients previously treated with osimertinib (registration no. jRCTs031190077).

DOI： 10.1111/1759-7714.13503

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AME Publishing Company  

Background: Whether hazard ratio (HR) of progression-free survival (HRpfs), odds ratio (OR) of response rate (ORrr), OR of disease control rate (ORdcr), and OR of 1-year overall survival (ORos1y) used for extensive-disease small-cell lung cancer (ED-SCLC) correlate with HR of overall survival (HRos) at a randomized-trial level, especially for a trial that evaluates molecular-targeted therapy (MTT) or immune-checkpoint inhibitor (ICI), is unclear. Methods: We included an individually randomized controlled trial (RCT) comparing two regimens as the first-line treatment for chemo-naive ED-SCLC, which have been reported in English-language since 2000. A weighted Spearman's rank correlation coefficient (r) was evaluated. Results: We finally found 42 eligible articles consisted of 11,478 cases. Estimated r with HRos were as followings: HRpfs (29 trial, 8,573 cases, r=0.87), ORrr (39 trials, 11,030 cases, r=0.47), ORdcr (29 trials, 7,799 cases, r=0.48), and ORos1y (40 trials, 11,250 cases, r=0.69). Phase III subgroup (16 trials, 7,079 cases) yielded an excellent r between HRpfs and HRos of 0.96. ORdcr presented the best correlation with HRos for phase II trial subgroup (r=-0.64); however, this result was mainly calculated from MTT trials. HRpfs may overestimate the efficacy of MMT in a phase II trial. ORrr and ORdcr might undervalue the efficacy of ICI even in a phase III trial. Conclusions: HRpfs can be a good surrogate of HRos, especially in a phase III trial. Depending on a single outcome in a randomized phase II trial may result in unneeded phase III trial or inappropriate abandonment of the regimen.

DOI： 10.21037/tlcr-20-377

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

A 50-year-old woman with stage IV lung adenocarcinoma received seven cycles of pembrolizumab as third-line chemotherapy. Following the failure of pembrolizumab, she commenced fourth-line chemotherapy of docetaxel and ramucirumab. The patient complained of epigastric pain and a computed tomography (CT) scan revealed oedema-like thickening of the gallbladder wall, dilation of the bile ducts from the common to the intrahepatic bile ducts, and thickening of the common bile duct wall without any visible obstructions. Accumulation of fluorodeoxyglucose (FDG) in the gallbladder wall and bile duct was also detected with positron emission tomography (PET)-CT. A biopsy of the extrahepatic bile duct showed non-specific inflammation. Antibiotic treatment was not effective and pathogens were not detected. The patient was diagnosed with secondary sclerosing cholangitis (SSC) by pembrolizumab. She received 80 mg/day of prednisolone (PSL); however, SSC recurred with tapering of PSL. SSC then improved with steroid pulse therapy and subsequently 50 mg/day azathioprine and 80 mg/day PSL.

DOI： 10.1002/rcr2.560

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) have an important role in lung cancer therapy. Although the programmed cell death protein-1 (PD-L1) tumor proportion score (TPS) and tumor mutational burden are known prognostic factors, they are insufficient to predict clinical outcomes. This study was conducted to identify novel biomarkers for ICI treatment. PATIENTS AND METHODS: We performed univariable and multivariable analyses of 110 patients with advanced non-small-cell lung cancer (NSCLC) who were treated with an ICI to identify novel biomarkers related to prognosis. We assessed their backgrounds, such as performance status (PS), PD-L1 TPS, smoking status, and peripheral white blood cell counts at baseline and on the day the second course of ICI administration. RESULTS: In the multivariable analysis, PS, driver gene, immune-related adverse events, and post-treatment absolute neutrophil counts (post-ANCs) were significantly associated with progression-free survival. CONCLUSION: A high level of post-ANCs was associated with poor outcome in ICI-treated NSCLC patients.

DOI： 10.21873/anticanres.14379

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

BACKGROUND: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF)-A, has shown efficacy in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). There are no identified or clinically validated biomarkers to determine the efficacy of bevacizumab. In this study, we assessed the adequacy of chemokine (C-X-C motif) ligand 16 (CXCL16) as a biomarker for patients treated with bevacizumab-containing chemotherapy regimen. METHODS: Patients diagnosed histologically with NSCLC were enrolled. Serial serum CXCL16 levels during treatment were measured by enzyme-linked immunosorbent assay. The relationship between serum CXCL16 levels before and after treatment, progression-free survival, and overall survival were analyzed. CXCL16 and VEGF-A expressions in lung cancer tissue were also evaluated by immunohistochemical tests. RESULTS: The median serum level of CXCL16 in these patients was 3.4 ng/mL, which was significantly higher than that in age-matched healthy adults (2.2 ng/mL). Immunohistochemistry results showed that CXCL16 was predominantly localized in the tumor stroma, whereas VEGF was expressed in tumor cells. Including bevacizumab with chemotherapy led to lower CXCL16 levels post-chemotherapy, which correlated with better response rates. In addition, evaluation of differences in serum CXCL16 levels before and after the first-line chemotherapy showed that longer overall survival was achieved in patients who showed a larger decrease in serum CXCL16 levels. CONCLUSIONS: According to our findings, serum CXCL16 level was identified as a potential biomarker for the efficacy of therapy, including anti-VEGF. KEY POINTS: Significant findings of the study Patients with NSCLC whose serum CXCL16 levels decreased below 0.07 ng/mL after chemotherapy, showed longer overall survival than those without this decrease. Moreover, low CXCL16 levels corresponded to better response rates among patients with advanced NSCLC treated with bevacizumab-containing chemotherapy. What this study adds Previously there were no identifiable predictive biomarkers to determine the efficacy of bevacizumab. Data from our findings identified serum CXCL16 level as a potential biomarker for the efficacy of bevacizumab-containing chemotherapy.

DOI： 10.1111/1759-7714.13387

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

BACKGROUND: Currently, anticancer immunotherapy based on PD-1/PD-L1 blockade with immune checkpoint inhibitors (ICIs) is being used as a standard therapy for non-small cell lung cancer (NSCLC). However, more effective treatments are required as these tumors are often resistant and refractory. Here, we aimed to determine the effects of immunomodulatory oligodeoxynucleotides (ODNs) in terms of the presence or absence of CpG motifs and the number of consecutive guanosines. METHODS: Western blots were used to measure the molecules which regulate the expression of PD-L1 in human lung cancer cell lines after incubation with several cytokines and ODNs. The expression of PD-L1 and β2-microglobulin (β2-MG) on A549 cells, and IFN-γ-induced apoptosis with ODNs were examined by flow cytometry. The relationship between IFN-γ receptor and ODN was analyzed by ELISA and immunofluorescence chemistry. RESULTS: Our results verified that A-CpG ODNs suppress the upregulation of IFN-γ-induced PD-L1 and β2-MG expression. In addition, we found that ODNs with six or more consecutive guanosines (ODNs with poly-G sequences) may competitively inhibit the IFN-γ receptor and abolish the effect of IFN-γ, thereby suppressing apoptosis and indoleamine 2,3-dioxygenase 1 expression in human lung cancer cells. The tumor microenvironment regulates whether this action will promote or suppress tumor immunity. Thus, in immunotherapy with CpG ODNs, it is essential to consider the effect of ODNs with poly-G sequences. CONCLUSIONS: This study suggests that ODNs containing six or more consecutive guanosines may inhibit the binding of IFN-γ to IFN-γ receptor. However, it does not directly show that ODNs containing six or more consecutive guanosines competitively inhibit the IFN-γ receptor, and further studies are warranted to confirm this finding. KEY POINTS: Significant findings of the study: Oligodeoxynucleotides with a contiguous sequence of six or more guanosines may competitively inhibit the IFN-γ receptor and abolish the action of IFN-γ. This may suppress IFN-γ-induced apoptosis and indoleamine-2,3-dioxygenase-1 expression in human lung cancer cells. WHAT THIS STUDY ADDS: A-CpG and poly-G ODN may overcome tolerance if the cause of ICI tolerance is high IDO expression. However, IFN-γ also has the effect of suppressing apoptosis of cancer cells, and it is necessary to identify the cause of resistance.

DOI： 10.1111/1759-7714.13351

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

OBJECTIVES: The interferon-gamma release assay (IGRA) is useful for diagnosing Mycobacterium tuberculosis infections, especially in countries where Bacille Calmette-Guérin vaccinations are performed. However, reproducibility of the IGRA is unclear, as recent data suggest high IGRA conversion and reversion rates in serial tests among healthcare workers. This longitudinal study aimed to evaluate reproducibility of T-SPOT.TB for screening M. tuberculosis infections in Japan. METHODS: Results of T-SPOT.TB tests performed between April 2014 and March 2016 at two hospitals in Yokohama, Japan, where the incidence of tuberculosis was 18.0 per 100,000 population in 2014, were analyzed. RESULTS: In total, 3890 T-SPOT.TB tests were included. Overall, positive and negative test rates were 8.4% and 87.6%, respectively. Among 373 serial tests within two years, conversion and reversion rates were only 1.1% and 12.5%, respectively. Almost all patients who were initially negative (98.9%) remained so. There was no statistically significant difference between the outcomes observed at the two hospitals. CONCLUSIONS: The conversion rate of T-SPOT.TB in Japan is as low as that recently reported in other countries where the incidence of tuberculosis is low. These data indicate that T-SPOT.TB is a reproducible tuberculosis screening tool at local hospitals in areas with a moderate incidence of tuberculosis.

DOI： 10.1016/j.jiac.2019.08.006

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Language：Japanese   Publisher：日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会  

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Language：Japanese   Publisher：日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会  

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Language：Japanese   Publisher：日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Massachusetts Medical Society  

DOI： 10.1056/nejmoa1913662

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

<sec><title>Background:</title> Our goal was to organize the data from randomized controlled trials that evaluated first-line chemotherapy for chemo-naïve extensive disease small-cell lung cancer (ED-SCLC).

</sec><sec><title>Methods:</title> The protocol following PRISMA methodology was submitted as PROSPERO 154049. We included individually randomized trials comparing two or more chemotherapy regimens as the first-line treatment for chemo-naïve ED-SCLC regardless of the age, sex, performance status, co-morbidities, and organ functions written in the English language since 2000. Molecular targeted agents and immune checkpoint inhibitors were considered chemotherapy along with cytotoxic medications. We pooled the logarithm of hazard ratio (HR) and its standard error using the frequentist weighted least squares approach random-model network meta-analysis.

</sec><sec><title>Results:</title> A total of 46 eligible trials that involved 11,987 patients were included. The primary endpoint, HR of overall survival (OS, HRos) of the selected comparisons was as follows: carboplatin+amrubicin (HRos 0.56, 95% confidence interval (CI) 0.33–0.96), carboplatin+etoposide+atezolizumab (HRos 0.70, 95% CI 0.53–0.92), and carboplatin+irinotecan (HRos 0.73, 95% CI 0.58–0.91) were compared with carboplatin+etoposide. The carboplatin+etoposide+atezolizumab regimen was compared with carboplatin+irinotecan (HRos 0.97, 95% CI 0.68–1.37) and cisplatin+irinotecan regimen (HRos 0.87, 95% CI 0.58–1.31). “Selective carboplatin or cisplatin (CBDCA/CDDP)”+etoposide+durvalumab was compared with CBDCA/CDDP+etoposide (HRos 0.73, 95% CI 0.59–0.91). Platinum+etoposide+durvalumab was compared with platinum+irinotecan (HRos 0.88, 95% CI 0.67–1.15). Cumulative meta-analysis suggested that platinum+irinotecan was associated with better OS than platinum+etoposide as of 2010 through 40 out of 46 trials in our review that used platinum+etoposide as a reference regimen.

</sec><sec><title>Conclusion:</title> Patients treated with carboplatin+amrubicin, carboplatin+etoposide+atezolizumab, CBDCA/CDDP+etoposide+durvalumab, and platinum+irinotecan showed better HRos than those treated with platinum+etoposide, one of the standard regimens.

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DOI： 10.1177/1758835920965841

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Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/1758835920965841

Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

An 82-year-old man with chronic tuberculous empyema visited our hospital for an annual computed tomography (CT) scan. No differences were noted between the CT scan at presentation and a scan performed a year previously in August 2017. He began experiencing right chest, epigastrium, and back pain since the end of October 2017. A CT scan taken in November of 2017 to evaluate the pain in his right chest, epigastrium, and back showed an irregular thickening of the pleura adjacent to the empyema and an abnormal right seventh costal mass infiltrating the vertebral body. CT-guided needle biopsy of the mass showed angiosarcoma. Positron emission tomography/CT revealed multiple metastases in his bones and liver. Chemotherapy was not recommended owing to his poor performance status, which was related to angiosarcoma. Therefore, he was offered palliative radiotherapy for the metastasis to the vertebral body.

DOI： 10.1002/rcr2.479

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

We report the case of an 85-year-old man who was surgically diagnosed with lung adenocarcinoma (pT2aN1M0 stage IIA). He was administered platinum combination chemotherapy as first-line treatment for lung cancer recurrence. The patient's pleural fluid sample was obtained and analysed using a next-generation sequencer, which demonstrated the presence of mesenchymal-epithelial transition gene (MET) exon 14 skipping mutations. As the patient developed progressive disease after receiving first-line chemotherapy, crizotinib was administered as the second-line treatment. The treatment was effective, and the patient had a stable disease for 7 months. This case suggests that crizotinib is effective against non-small cell lung cancer with MET exon 14 alterations.

DOI： 10.1002/rcr2.453

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

OBJECTIVES: A major regulatory peptide in iron metabolism, hepcidin, has been shown to predict mortality in HIV-infected tuberculosis patients. The aim of this study was to evaluate whether plasma hepcidin levels on admission can be used to predict the treatment outcome of patients with smear-positive pulmonary tuberculosis (PTB) without HIV co-infection. METHODS: In this prospective observational study, a total of 35 PTB patients with Mycobacterium tuberculosis-positive sputum smears were enrolled. The relationship between plasma hepcidin levels on admission and the time period to sputum culture-negative was explored. RESULTS: Plasma hepcidin levels of PTB patients were significantly higher than those of healthy subjects (p<0.001). A positive correlation between hepcidin level on admission and the period until culture-negative was also observed (r=0.46, p=0.006). Furthermore, the hepcidin level showed a negative correlation with spot numbers in the positive control wells of the T-SPOT.TB assay; thus the effect of the peptide on interferon-gamma production in T cells was explored. Hepcidin reduced interferon-gamma gene transcription and interferon-gamma production in a dose-dependent manner in Jurkat cells stimulated with phytohaemagglutinin, an antigen non-specific stimulation. CONCLUSIONS: These findings indicate that hepcidin alters immunological reactions against M. tuberculosis infection and has an influence on the outcomes of PTB patients without HIV co-infection.

DOI： 10.1016/j.ijid.2019.06.023

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：日本結核病学会関東支部学会・日本呼吸器学会関東地方会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：日本結核病学会関東支部学会・日本呼吸器学会関東地方会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：神奈川県医師会  

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Background: A prognostic factor for patients with acute or subacute idiopathic interstitial pneumonias (IIPs) or acute exacerbation (AE) of collagen vascular diseases-related interstitial pneumonia (CVD-IP) has not been established. We aimed to determine whether the Charlson comorbidity index (CCI) could serve as a prognostic factor for patients with these patients. Methods: We assessed baseline prognostic factors among patients with acute or subacute IIPs and AE of CVD-IP who were admitted to hospital between January 2014 and December 2017. We classified them as survivors and non-survivors at 3 months and compared their age, sex, CCI, blood parameters [lactate dehydrogenase (LDH), surfactant protein (SP)-D, Krebs von den Lungen-6, and partial pressure of oxygen in arterial blood/fraction of the inspiratory oxygen], high resolution CT (HRCT) scores and treatment. Results: Sixty eight patients with (mean age, 75 years), were assessed. All patients received steroid pulse therapy. We found that 45 of acute or subacute IIPs and 16 of AE of CVD-IP were included. Stepwise multivariate analysis selected CCI (OR, 1.306; 95% CI, 1.090-1.573; P=0.004), serum LDH (OR, 1.003; 95% CI, 1.001-1.005; P=0.002), and sex (OR, 8.555; 95% CI, 1.729-154.978; P=0.038) as significant predictors of 3-month mortality among these patients. Three-month mortality was significantly worse among patients with high (≥4) than low (<4) CCI (mortality rates: 63.2% vs. 16.3%, P<0.001). Moreover, the composite scoring system including CCI, serum LDH, and sex was acceptable (Bootstrap AUC, 0.859; Bootstrap C-index, 0.747). Conclusions: The composite scoring system including CCI, sex, and serum LDH could be a useful mortality prediction tool for patients with acute or subacute IIPs and AE of CVD-IP requiring steroid pulse therapy.

DOI： 10.21037/jtd.2019.05.46

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：日本結核病学会関東支部学会・日本呼吸器学会関東地方会  

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Language：Japanese   Publisher：日本結核病学会関東支部学会・日本呼吸器学会関東地方会  

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Language：Japanese   Publisher：横浜市立大学医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01499&link_issn=&doc_id=20190711360003&doc_link_id=http%3A%2F%2Fid.nii.ac.jp%2F1246%2F00001679%2F&url=http%3A%2F%2Fid.nii.ac.jp%2F1246%2F00001679%2F&type=%89%A1%95l%8Es%97%A7%91%E5%8Aw%81F%89%A1%95l%8Es%97%A7%91%E5%8Aw%8Aw%8Fp%8B%40%8A%D6%83%8A%83%7C%83W%83g%83%8A&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80205_3.gif

Language：Japanese   Publisher：日本結核病学会関東支部学会・日本呼吸器学会関東地方会  

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Language：Japanese   Publisher：(公社)日本化学療法学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Massachusetts Medical Society  

BACKGROUND: Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. We compared osimertinib with standard EGFR-TKIs in patients with previously untreated, EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). METHODS: In this double-blind, phase 3 trial, we randomly assigned 556 patients with previously untreated, EGFR mutation-positive (exon 19 deletion or L858R) advanced NSCLC in a 1:1 ratio to receive either osimertinib (at a dose of 80 mg once daily) or a standard EGFR-TKI (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily). The primary end point was investigator-assessed progression-free survival. RESULTS: The median progression-free survival was significantly longer with osimertinib than with standard EGFR-TKIs (18.9 months vs. 10.2 months; hazard ratio for disease progression or death, 0.46; 95% confidence interval [CI], 0.37 to 0.57; P<0.001). The objective response rate was similar in the two groups: 80% with osimertinib and 76% with standard EGFR-TKIs (odds ratio, 1.27; 95% CI, 0.85 to 1.90; P=0.24). The median duration of response was 17.2 months (95% CI, 13.8 to 22.0) with osimertinib versus 8.5 months (95% CI, 7.3 to 9.8) with standard EGFR-TKIs. Data on overall survival were immature at the interim analysis (25% maturity). The survival rate at 18 months was 83% (95% CI, 78 to 87) with osimertinib and 71% (95% CI, 65 to 76) with standard EGFR-TKIs (hazard ratio for death, 0.63; 95% CI, 0.45 to 0.88; P=0.007 [nonsignificant in the interim analysis]). Adverse events of grade 3 or higher were less frequent with osimertinib than with standard EGFR-TKIs (34% vs. 45%). CONCLUSIONS: Osimertinib showed efficacy superior to that of standard EGFR-TKIs in the first-line treatment of EGFR mutation-positive advanced NSCLC, with a similar safety profile and lower rates of serious adverse events. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125 .).

DOI： 10.1056/nejmoa1713137

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.0138-17

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Language：Japanese   Publisher：日本職業・環境アレルギー学会  

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/srep46488

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：English  

DOI： 10.1186/s12931-018-0852-6

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.2169/internalmedicine.9120-17

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Currently, amrubicin is permitted for relapsed small-cell lung carcinoma (SCLC) only in Japan. The efficacy and adverse effects of amrubicin as reported by previous studies varied greatly. The inclusion criterion was a prospective study that was able to provide data for efficacy and safety by the AMR single agent regimen as second-line chemotherapy for a patient with SCLC. Binary data were meta-analyzed with the random-model generic inverse variance method. We included nine articles consisted of 803 patients. The pooled three-, six-, and nine-month progression-free survival were 63% (95% CI 57-69%, I-2 = 53%), 28% (95% CI 21-35%, I-2 = 71%), and 10% (95% CI 6-14%, I-2 = 41%), respectively. The pooled six-, 12-, and 18-month overall survival were 69% (95% CI 61-78%, I-2 = 83%), 36% (95% CI 28-44%, I-2 = 80%), and 15% (95% CI 8-21%, I-2 = 81%), respectively. Amrubicin seemed much more beneficial for Japanese patients. However, compared to the efficacy of topotecan presented in a previous meta-analysis, amrubicin may be a better treatment option than topotecan for both Japanese and Euro-American. Adverse effects by amrubicin were almost exclusively observed to be hematological. Notably, grade III/IV neutropenia incidence was 70% and febrile neutropenia incidence was 12%.

DOI： 10.1038/srep18999

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Language：English   Publisher：AMER THORACIC SOC  

DOI： 10.1038/srep18999

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.36.Special_S225_3

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.36.Special_S246_1

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.4049/jimmunol.1201063

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DOI： 10.2169/internalmedicine.52.0701

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.61.1476_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.61.1476_3

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10156-009-0020-5

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Language：English   Publishing type：Research paper (scientific journal)  

Recently, we reported that a complex with an essential role in the degradation of Fructose-1,6-bisphosphatase in yeast is well conserved in mammalian cells; we named this mammalian complex C-terminal to the Lissencephaly type-1-like homology (CTLH) complex. Although the function of the CTLH complex remains unclear, here we used yeast two-hybrid screening to isolate Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) as a protein binding to a key component of CTLH complex, Armadillo repeat containing 8 (ARMc8) alpha. The association was confirmed by a yeast two-hybrid assay and a co-immunoprecipitation assay. The proline-rich domain of HRS was essential for the association. As demonstrated through immunofluorescence microscopy, ARMc8alpha co-localized with HRS. ARMc8alpha promoted the interaction of HRS with various ubiquitinated proteins through the ubiquitin-interacting motif. These findings suggest that HRS mediates protein endosomal trafficking partly through its interaction with ARMc8alpha.

DOI： 10.2174/1874091X01004010001

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Language：Japanese  

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CiNii Books

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J03150&link_issn=&doc_id=20090223290011&doc_link_id=10024823613&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F10024823613&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.58.1235_3

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.31.5_338_3

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1042/BJ20071312

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DOI： 10.1016/j.gene.2007.02.032

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.56.1187_3

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese  

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2004&ichushi_jid=J00298&link_issn=&doc_id=20040608230026&doc_link_id=%2Fcf0brond%2F2004%2F002604%2F027%2F0391-0391%26dl%3D2&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcf0brond%2F2004%2F002604%2F027%2F0391-0391%26dl%3D2&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_5.gif

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Language：English   Publishing type：Research paper, summary (international conference)  

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Language：English   Publishing type：Research paper, summary (international conference)  

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Language：English   Publishing type：Research paper, summary (international conference)  

DOI： 10.1158/1538-7445.AM2014-2576

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J00298&link_issn=&doc_id=20140415290165&doc_link_id=%2Fcf0brond%2F2014%2F0036s1%2F0a6%2F5177-5177%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcf0brond%2F2014%2F0036s1%2F0a6%2F5177-5177%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper, summary (international conference)  

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Language：English   Publishing type：Research paper, summary (international conference)  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：日本肺癌学会  

CiNii Books

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会