Maintaining Weight and Nutritional Status with Ninjin'yoeito in Elderly Patients with Chronic Wasting Diseases.

Objectives: This retrospective study aimed to obtain information on the nutritional maintenance effects of Ninjin'yoeito (NYT) in elderly patients with chronic wasting diseases. Methods: Changes in body weight and serum levels of total protein and albumin were investigated in patients who received NYT for chronic wasting diseases for more than six months in Mito Medical Centre, University of Tsukuba-Mito Kyodo General Hospital, Mito, Japan, from April 2009 to October 2019. Results: During the study period, 11 patients (median age: 75 years) received NYT for six months or more. The median administration period of NYT was 14 months. The body weight and serum levels of total protein and albumin at the time of the last observation were not significantly different from those at the beginning of NYT administration (P = 0.176, P = 0.766 and P = 0.550, respectively). Conclusion: This study suggested the possibility of maintaining nutritional condition by administering NYT in elderly patients with chronic wasting disease of various aetiologies. More evidence will be required to confirm these results.

Body Weight Change in Non-small Cell Lung Cancer Patients Treated With EGFR-TKI.

BACKGROUND/AIM: Body weight (BW) changes in epidermal growth factor inhibitor-tyrosine kinase (EGFR-TKI) treated non-small cell lung cancer patients has yet to be fully investigated. For the purpose of clarifying changes in body weight in patients who received EGFR-TKI treatment in clinical practice, we performed a retrospective study. In this study, comparison between pretreatment BW and those at 12, 24 weeks, and 12 months in these patients was performed. PATIENTS AND METHODS: We included all the patients diagnosed with EGFR mutated NSCLC in two tertiary hospitals between April 2009 and March 2021. BW records in the medical chart of each patient who was treated with EGFR-TKI for more than 12 weeks were surveyed. In each patient, BW at 12, 24 weeks, and 12 months from the initiation of EGFR-TKI treatment were compared with pretreatment BW. RESULTS: Sixty-three patients obtained TKI treatment for more than 12 weeks and had comparable body weight records. Compared with the pretreatment BW, decreased BW was observed at 12, 24 weeks, and 12 months from the initiation of TKI treatment. CONCLUSION: Even in patients treated with EGFR-TKI, which is evaluated as less toxic and a more effective therapy, there might be patients who lose weight during the treatment period. Chest physicians will be required to provide medical care even for EGFR mutated patients, taking into consideration changes in BW.

Common exacerbation-prone phenotypes across asthma and chronic obstructive pulmonary disease (COPD).

BACKGROUND AND OBJECTIVES: Chronic inflammatory airway diseases, including asthma and chronic obstructive pulmonary disease (COPD), are complex syndromes with diverse clinical symptoms due to multiple pathophysiological conditions. In this study, using common and shared risk factors for the exacerbation of asthma and COPD, we sought to clarify the exacerbation-prone phenotypes beyond disease labels, and to specifically investigate the role of the IL4RA gene polymorphism, which is related to type 2 inflammation, in these exacerbation-prone phenotypes. METHODS: The study population comprised patients with asthma (n = 117), asthma-COPD overlap (ACO; n = 37) or COPD (n = 48) and a history of exacerbation within the previous year. Cluster analyses were performed using factors associated with both asthma and COPD exacerbation. The association of the IL4RA gene polymorphism rs8832 with each exacerbation-prone phenotype was evaluated by multinomial logistic analyses using non-asthma non-COPD healthy adults as controls (n = 1,529). In addition, the genetic influence of rs8832 was also examined in asthma patients with allergic rhinitis and no history of exacerbation (n = 130). RESULTS: Two-step cluster analyses identified five clusters that did not necessarily correspond to the diagnostic disease labels. Cluster 1 was characterized by high eosinophil counts, cluster 2 was characterized by smokers with impaired lung function, cluster 3 was characterized by the presence of gastroesophageal reflux, cluster 4 was characterized by non-allergic females, and cluster 5 was characterized by allergic rhinitis and elevated total immunoglobulin E levels. A significant association with rs8832 was observed for cluster 5 (odds ratio, 3.88 (1.34-11.26), p = 0.013) and also for the type 2 exacerbation-prone phenotypes (clusters 1 and 5: odds ratio, 2.73 (1.45-5.15), p = 1.9 × 10-3). DISCUSSION: Our results indicated that the clinical heterogeneity of disease exacerbation may reflect the presence of common exacerbation-prone endotypes across asthma and COPD, and may support the use of the treatable traits approach for the prevention of exacerbations in patients with chronic inflammatory airway diseases.

Response to erlotinib and bevacizumab combination therapy after acquired resistance to osimertinib in patients with non-small cell lung cancer.

Osimertinib is the most reliable epidermal growth factor receptor-tyrosine kinase (EGFR-TKI) and is recommended as the first-line EGFR-TKI. Therefore, developing acquired resistance to this TKI might be problematic because no appropriate treatment with TKIs has been established after acquired resistance to osimertinib. For patients with osimertinib resistance, antitumor drugs having different mechanism from that of EGFR-TKI are usually prescribed. However, these treatments do not include the effective utilization of several EGFR-TKIs for these patients. We herein report two cases of response to erlotinib and bevacizumab combination therapy after acquired resistance to osimertinib in patients with non-small cell lung cancer. Although the precise biological mechanism is unknown, this combination therapy may be an option for some patients who suffer from acquired resistance to osimertinib.

Nintedanib-mediated improvement in CT imaging in pulmonary fibrosis associated with systemic scleroderma.

Nintedanib is an antifibrotic drug that has an inhibitory effect on growth factor tyrosine kinases. In patients with idiopathic pulmonary fibrosis and systemic scleroderma-associated interstitial pneumonia (SSc-IP), nintedanib has been effective in suppressing the decline in forced vital capacity over time and the onset of acute exacerbation of interstitial pneumonia. Here, we report a SSc-IP patient who showed an improvement on CT images following nintedanib treatment. To our knowledge, this is the first report of such a case. Although SSc-IP patients are very rare, additional clinical experience and understanding will be required to prove the therapeutic benefit of nintedanib in these cases in relation to improved chest images.

Pseudoprogression during successful rechallenge of immune checkpoint inhibitor in a NSCLC patient.

Rechallenge of immune checkpoint inhibitors (ICPIs) is one of the attractive but unestablished treatment for recurrent non-small cell lung cancer (NSCLC) patients who have been treated with several-lines of systemic chemotherapy. In some NSCLC patients, effects of ICPI rechallenge therapy have become apparent. In ICPI treatment, although very rare, a phenomenon called pseudoprogression is known. We report the first case of a patient who had pseudoprogression during successful rechallenge of ICPI in a NSCLC patient. Although not fully clarified, factors related to the onset of pseudoprogression and good response to ICPI rechallenge are being investigated. Our case showed that pseudoprogression could be developed even in patients with ICPI rechallenge therapy.

A tracheobronchial adenoid cystic carcinoma incidentally detected by chest radiography and pulmonary function test.

Tracheobronchial adenoid cystic carcinomas are rare tumors that progress slowly.　Diagnosis by chest plain radiography is difficult, and suspecting the existence of a disease that causes stenosis in the airways is an important key for diagnosis. A 51-year-old woman referred to our hospital because of dyspnea on exertion. Chest plain radiograph showed a slight widening of the mediastinum. The flow-volume curve of respiratory function test revealed flat portions of the curve suggesting the central airway obstruction pattern. Chest CT confirmed the existence of tracheobronchial tumor, which was pathologically diagnosed as adenoid cystic carcinoma. Chest physicians and thoracic surgeons should be careful not to miss these trivial findings in the first inspections.

Association between time to treatment failure and peripheral eosinophils in patients with non-small cell lung cancer treated with immune checkpoint inhibitors.

Introduction: There is an unmet clinical need to identify biomarkers predicting which patients with non­small cell lung cancer (NSCLC) would benefit from treatment with immune checkpoint inhibitors (ICPIs). Objectives: The purpose of this study was to draw a detailed time to treatment failure (TTF) curve with information on the changes in peripheral eosinophil expression during ICPI treatment for NSCLC, and to clarify whether eosinophil expression can predict prolonged TTF. Patients and methods: In 259 patients with NSCLC treated with ICPI therapy, peripheral eosinophil counts and percentages at the time of each ICPI administration were evaluated from the beginning of ICPI treatment up to TTF. Univariable and multivariable analyses were performed to identify clinical factors associated with TTF. Results: Patients receiving ICPI monotherapy (n = 180) were divided into 3 groups (TTF ≤6 weeks, TTF >6 weeks and ≤24 weeks, and TTF >24 weeks) and the number of patients with an eosinophil percentage of 5% or more within 6 weeks of ICPI therapy initiation was significantly different among these groups. In univariable and multivariable analyses, performance status of 0 to 1, immune-related adverse event not requiring ICPI discontinuation as well as an eosinophil percentage of 5% or more and an eosinophil count of 330/µ or more within 6 weeks of ICPI therapy initiation were significant favorable factors for prolonged TTF. In patients treated with combination therapy of ICPI and chemotherapy (n = 79), the number of patients with an eosinophil percentage of 5% or more within 12 weeks of therapy initiation was significantly different between patients with a TTF of up to 12 weeks and those with a more prolonged TTF. However, the only significant favorable factor for TTF was female sex. Conclusions: In NSCLC patients treated with ICPI therapy, particularly ICPI monotherapy, eosinophil measurements during treatment might be useful for predicting prolonged TTF.

Imaging characteristics of nontuberculous mycobacterial pulmonary nodules.

Introduction. Nontuberculous mycobacteriosis (NTM) of the lungs can develop nodules. In order to clarify some of the characteristics of lung NTM nodules, we examined volume doubling time (VDT) and maximum standardized uptake value (SUVmax) in positron emission tomography (PET) of pathologically diagnosed NTM nodules. Methods. From November 2012 to August 2018, clinical and radiological information were retrospectively investigated in eight patients who were surgically resected and diagnosed as NTM. These eight patients were followed up until November 2020 and were confirmed to have no appearance of lung cancer or reappearance of lung NTM nodules. The VDT was calculated using the Schwartz formula. Results. The median maximum diameter of the nodule at the time of the first CT scan was 16.0 (range: 9.9-20.0) mm. The median maximum diameter of the nodule on CT performed before the surgical biopsy was 18.8 (range: 10.4-32.8) mm. The median doubling time calculated from these results was 203 (range: 20-568) days. Caseous granulomas and acid-fast bacilli were histologically confirmed in all eight patients. Culture of excised nodules revealed Mycobacterium intracellulare in five patients and Mycobacterium avium in three patients. Six patients received PET, and median SUVmax was: 7.0 (range: 3.3-21.0). Median VDT was around 200 days. Some patients had irregular-shaped nodules. Conclusions. CT/PET-CT characteristics of lung nodules are not reliable in differentiating lung NTM nodules from malignant ones. To avoid unnecessary resection, it may be better to collect various information on imaging findings in the nodule itself and in opacities other than the nodule.

Changes in Body Weight and Serum Albumin Levels in Patients Requiring Home Long-term Oxygen Therapy.

Purpose: To investigate the long-term changes in body weight and serum albumin levels in patients with respiratory failure, and those with chronic heart failure, who were treated with home long-term oxygen therapy (LTOT) to understand the current status and contribute to future measures. Methods: Patients with chronic obstructive pulmonary disease (COPD), those with interstitial pneumonia (IP), and those with chronic heart failure (CHF) undergoing home LTOT for 6 months or more between January 2011 and January 2019 were included in the study. Body weight and serum albumin levels were assessed at the start of home LTOT and at the end of the observation period, a minimum of 6 months after commencing home LTOT. Results: Sixty-two patients (29 COPDs, 23 IPs, and 10 CHFs) were included. In COPD patients and IP patients, body weight decreased (P = 0.0017, P = 0.0018, respectively, Wilcoxon signed-rank test). Serum albumin levels decreased in IP patients (P = 0.0185) but not in COPD patients. There was neither significant decrease in body weight nor serum albumin levels in patients with CHF. Conclusion: Chronic respiratory failure patients who have home LTOT were likely to have a decreased nutritional status. In order to provide prolonged home LTOT, medical staff need to pay close attention to the nutritional status of patients receiving home LTOT.

Effect of Shakuyakukanzoto on Chemotherapy-Induced Hiccups in Patients with Lung Cancer.

OBJECTIVE: Shakuyakukanzoto, one of the traditional herbal medicines commonly used in North-East Asian countries, is known to be effective for muscle cramps. This retrospective study aimed to evaluate the effect of shakuyakukanzoto on chemotherapy-induced metoclopramide-uncontrolled hiccups. MATERIALS AND METHODS: We retrospectively investigated the medical records of all the consecutive patients with lung cancer who were prescribed with shakuyakukanzoto (Tsumura Co. Tokyo, Japan) for chemotherapy-induced hiccups in our hospital from September 2013 to November 2017. In the medical record from the initiation of shakuyakukanzoto until the start of the next chemotherapy, when there was description of "complete or partial disappearance of hiccups" after the prescription of shakuyakukanzoto, it was judged as a complete or partial response. A statement of "unchanged," no description of improvement, or exacerbation was judged as no change. RESULTS: Of the 49 chemotherapy courses in 15 patients with lung cancer, 93.9% had a "partial or complete" response within a few hours after the administration of shakuyakukanzoto. The effect of shakuyakukanzoto was observed irrespective of the pathological type of lung cancer, platinum-containing or non-platinum chemotherapy, and with or without other anti-hiccup drugs. No adverse event was observed. CONCLUSION: Shakuyakukanzoto may offer an effective pharmacological approach to treat chemotherapy-induced metoclopramide-uncontrolled hiccups. Well-planned prospective studies will confirm our results.

Association between peripheral eosinophils and clinical outcomes in patients with non-small cell lung cancer treated with immune checkpoint inhibitors.

INTRODUCTION: Programmed cell death ligand 1 is considered a predictor of the therapeutic effect of immune checkpoint inhibitors (ICPIs), but a more simple and useful predictor is needed. OBJECTIVES: The aim of this study was to identify the relationship between eosinophil counts and percentages and response to ICPI therapy. PATIENTS AND METHODS: In 190 patients with non-small cell lung cancer (NSCLC) treated with ICPI therapy, peripheral eosinophil counts and percentages at the time of ICPI therapy initiation, the maximum counts and percentages of eosinophils during ICPI therapy, response to therapy, and time to treatment failure (TTF) were investigated. RESULTS: Both an increase in the peripheral eosinophil count and an elevation of eosinophil percentage following the initiation of ICPI therapy were observed, regardless of whether the patients had controlled or progressive disease. The median time to the maximum eosinophil percentage was 5 weeks in patients with controlled disease and 2 weeks in those with progressive disease. The cutoff value for the maximum eosinophil counts and percentage during ICPI therapy was set at 300/µl and 5%, respectively, to identify the presence or absence of a therapeutic effect. Time to treatment failure was longer in patients with maximum eosinophil counts exceeding 300/µl and a maximum eosinophil percentage above 5%. In a multivariable analysis, a maximum eosinophil percentage of 5% during ICPI therapy was a significant predictive factor for therapeutic efficacy. CONCLUSIONS: The measurement of peripheral eosinophils up to around 5 weeks following the initiation of treatment, especially the maximum eosinophils count and percentage, might provide useful information about the efficacy of ICPIs.

Absolute Increase in the Number and Proportion of Peripheral Eosinophils Associated With Immune Checkpoint Inhibitor Treatment in Non-small Cell Lung Cancer Patients.

Background/Aim: To clarify the clinical significance of the absolute increase in the number and proportion of peripheral eosinophils associated with immune checkpoint inhibitor (ICPI) treatment in non-small cell lung cancer (NSCLC) patients. Patients and Methods: We performed a retrospective study, by reviewing the medical charts of 191 patients who were treated with ICPI monotherapy and 80 patients treated with the combination of ICPI and chemotherapy during the period from February 2016 and April 2021. Results: In patients treated with ICPI monotherapy, there was a significant difference in time to treatment failure (TTF) between the two groups divided by eosinophils ≥ or <10%. Similarly, a significant difference was found in TTF between the two groups divided by eosinophils ≥ or <1,500/µl. Factors related to both an increase in the number and percentage of peripheral eosinophils were "immune-related adverse effects (irAE) that did not lead to discontinuation of administration". Conclusion: Some patients with irAE might have a 'favorable' absolute increase in peripheral eosinophils.