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Background: Biomarker assessments for nivolumab monotherapy efficacy in previously treated patients with non-small cell lung cancer (NSCLC) remain unclear. We evaluated whether body mass index (BMI) and Glasgow prognostic score (GPS) are useful for assessing the efficacy of nivolumab alone as a second-line treatment in patients with pretreated NSCLC., Methods: Data of 99 patients treated with second-line nivolumab monotherapy for NSCLC between January 2016 and December 2019 were evaluated for prognostic values of BMI and GPS to assess their usefulness in predicting progression-free survival (PFS) and overall survival (OS)., Results: The Eastern Cooperative Oncology Group-performance status (PS) independently predicted the second-line nivolumab monotherapeutic effect; good PS (0-1) correlated with significantly longer PFS (4.3 vs. 1.9 months, log-rank; p = 0.0004) and OS (17.7 vs. 4.6 months, log-rank; p < 0.0001) than poor PS. BMI independently predicted survival, with high BMI (≥22.1 kg/m 2 ) associated with significantly longer OS (19.1 vs. 8.5 months, log-rank; p = 0.0023) than low BMI (<22.1 kg/m 2 ). However, GPS showed no significant difference for PFS or OS., Conclusion: Among patients with NSCLC treated with nivolumab monotherapy as second-line treatment, PS was significantly correlated with both PFS and OS and BMI with OS. Thus, BMI could be a useful predictor of survival in these patients., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Yellow nail syndrome (YNS) is a rare disease comprising the clinical triad of yellow nail discoloration, pleural effusion, and lower limb lymphedema. We encountered a difficult-to-treat case of YNS in which the diagnosis was finally made based on intranodal lymphangiography. An 84-year-old man was admitted to our hospital with pleural effusion and yellow-green discoloration of the nails, accompanied by onychomycosis and limb lymphedema. Intranodal lymphangiography revealed a slow contrast flow and narrowing of the thoracic duct, suggesting lymphatic duct dysplasia and leading to the diagnosis of YNS.

Background: Allergen immunotherapy (AIT) is a specific treatment of administering clinically important allergens to patients who have allergic diseases. In Japan, the standardized house dust mite (HDM) allergen for subcutaneous immunotherapy (SCIT) was approved in 2015, and we then introduced rush-immunotherapy (rush-IT) using the standardized HDM allergen for HDM-sensitive asthmatics. However, little data are available on the safety and effectiveness of rush-HDM-IT, especially for Japanese asthmatics., Objective: The objective of this study was to examine the safety and clinical effectiveness of rush-IT using the standardized HDM for HDM-sensitive Japanese asthmatics., Methods: Thirteen HDM-sensitive asthmatics who received rush-HDM-IT and 12 HDM-sensitive asthmatic controls were enrolled. To evaluate the safety, the number of systemic reaction (SR) events, including anaphylaxis, was assessed. To evaluate the effectiveness, changes in the treatment step, dose of inhaled corticosteroid, and asthma control after rush-HDM-IT and the subsequent maintenance SCIT were assessed. Changes in the HDM-induced production of type 2 cytokines from peripheral blood mononuclear cells were also evaluated., Results: Among the 12 patients who received rush-IT, 4 (30.7%) experienced a SR and 3 (23.1%) experienced anaphylaxis. However, the anaphylaxis was not severe (grade 3) in all cases, and they recovered in a short time. The treatment step of asthma was better and the dose of inhaled corticosteroid was lower in the rush-HDM-IT group than in the control group. The HDM-induced production of both interleukin (IL)-5 and IL-13 from peripheral blood mononuclear cells was significantly lower in the rush-HDM-IT group than in the control group., Conclusion: Rush-HDM-IT can be performed relatively safely in Japanese asthmatics. Furthermore, rush-HDM-IT and the subsequent maintenance SCIT provided clinical improvement in asthma patients, and was accompanied by the suppression of HDM-specific Th2-mediated systemic immune responses., Competing Interests: Conflict of Interest: MN received fees for speaking from Torii Pharmaceutical Co., Ltd. The rest of the authors declare no conflicts of interest., (Copyright © 2021. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Background: Severe asthma is a complex disease with heterogeneous features and involves type 2 airway inflammation, including eosinophil accumulation. Surrogate biomarkers, fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (b-EOS), may predict eosinophilic airway inflammation. Here we investigated clinical characteristics of severe asthma phenotype using a combined analysis of FeNO and b-EOS., Methods: This retrospective study examined clinical data of patients with severe asthma (N = 107; median age, 64 years) treated at Saitama Medical University Hospital from 2009 to 2016. Thresholds of FeNO and b-EOS for sputum eosinophil ratio ≥2% were determined using receiver operating characteristic curve (ROC) analysis. Clinical characteristics were analyzed after classifying patients into four subgroups according to these thresholds., Results: Of 39 induced sputum samples examined, ROC area under the curve for predicting sputum eosinophilia was 82.0% (p = 0.001) for b-EOS and 77.0% (p = 0.006) for FeNO at optimal cut-off values of ≥300/μL and ≥25 ppb, respectively. The number of sensitized allergens was higher in the high FeNO/low b-EOS and high FeNO/high b-EOS subgroups (p < 0.05). The prevalence of chronic sinusitis was higher in the low FeNO/high b-EOS and high FeNO/high b-EOS subgroups (p = 0.04). The high FeNO/high b-EOS subgroup included the largest proportion (approximately 40%) of patients experiencing frequent severe exacerbations. Both low FeNO/low b-EOS and high FeNO/low b-EOS subgroups showed less severe exacerbations., Conclusions: Combined evaluation of FeNO and b-EOS can identify patients with frequent exacerbations and stratify the appropriate therapy for type 2 inflammation-predominant severe asthma., (Copyright © 2018 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Hematopoietic responses to environmental factors are not fully characterized. Polycythemia has been reported during exposure to low temperatures in ectothermic animals. The relationship between the causes of polycythemia and erythropoiesis during low temperature exposure is not fully understood. In this study, we exposed C57BL/6 mice to 5°C and monitored the blood cell counts and erythropoiesis. The hematocrit level increased from 45.6 to 52.2% after 14 days. Likewise, the hemoglobin concentration, initially 15.1 g dl(-1), rose to 16.0 g dl(-1). The reticulocyte production index significantly increased from 4 to 8% after 7 days. We examined the anatomy and cell composition of the spleens of the mice. On day 5, the spleens were ∼6 mg g(-1) of body mass, which was twofold greater than the spleens on day 0. Flow cytometry showed fourfold more proerythroblasts on day 5, compared with day 0. Additionally, the number of late-stage mature erythroblasts increased on day 14. Erythropoietin mRNA levels increased in the kidneys, and hypoxia-inducible genes were enhanced in the kidney. Our findings indicated that low ambient temperature is a novel erythropoietic stress, which induces polycythemia by enhanced erythropoiesis.

Diminished erythrocyte count and erythropoiesis have been reported during hypothermia in some ectothermic animals. In this study, the African clawed frog, Xenopus laevis, was used to investigate the cause of hypothermia-induced anemia. We developed a new model of hypothermia at 5°C and monitored blood cell count and erythropoiesis on several days. Erythrocyte count declined by 30% on the first day following cold exposure (5°C) and mRNA expression of hemeoxygenase-1 was enhanced 10-fold; accumulation of iron as a result of heme degradation was observed in the liver. One day after low-temperature exposure, erythropoietin mRNA expression was elevated in the liver and lung compared with that at normal temperature (22°C) by qRT-PCR analysis. Examination of liver sections (i.e. the erythropoietic organ) showed an increase in o-dianisidine-positive erythrocytes in the hepatic sinusoid 5 days after the onset of low-temperature exposure compared with normal liver. Peripheral erythrocyte count remained low, indicating that newly produced erythrocytes did not migrate from the liver to the circulation during hypothermia. In conclusion, this study reveals hypothermic anemia as being associated with hepatic erythrocyte destruction; prolonged anemia during low-temperature exposure is concomitant with newly produced erythrocytes being confined to the liver and may lead to new insights into vertebrate hematopoiesis.