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Objectives: This study aimed to assess the intrinsic impacts of the expression of PD-L1 on postoperative recurrence and the prognosis in patients with epidermal growth factor receptor ( EGFR )-mutated lung adenocarcinomas., Patients and Methods: Data from 221 surgically resected pathological stage IA-IIIA lung adenocarcinomas, collected between 2017 and 2019, were analyzed. This included measurements of EGFR mutations and the PD-L1 expression. Recurrence-free survival (RFS) and overall survival (OS) were estimated using a Kaplan-Meier analysis and log-rank test. The independent risk factors for RFS were assessed using univariate and multivariate analyses., Results: Among the patients, 140 were PD-L1-negative (<1%), while 81 were PD-L1-positive (≥1%). PD-L1 positivity was significantly associated with male sex (p=0.038), smoking habit (p=0.005), ND2 lymph node dissection (p=0.013), higher malignant subtype (p=0.003), higher histological grade (p=0.001), and advanced pathological stage (p=0.004). Conversely, EGFR mutations were more common in the PD-L1-negative group than in the PD-L1-positive group (p=0.006). Patients were categorized into four groups based on their EGFR mutation status and PD-L1 expression status: PD-L1-positive (≥1%) with or without EGFR mutations ( EGFR (+)/PD-L1≥1% or EGFR ( -)/PD-L1≥1%), and PD-L1-negative (<1%) with or without EGFR mutations ( EGFR (+)/PD-L1<1% or EGFR ( -)/PD-L1<1%). Among these groups, EGFR (+)/PD-L1≥1% cases exhibited the worst 5-year RFS (log-rank, p=0.010), while there was no significant difference in 5-year OS (log-rank, p=0.122). Furthermore, a multivariate analysis revealed that PD-L1 positivity was an independent significant factor for RFS in EGFR -mutated lung adenocarcinoma (p=0.013)., Conclusion: PD-L1 positivity emerged as an independent risk factor for RFS in patients with EGFR -mutant resected lung adenocarcinoma. These findings may provide valuable insights into the prognostic impact of PD-L1 expression and guide the implementation of postoperative adjuvant therapy in this patient population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ito, Kano, Tarukawa, Suzuki, Sakaguchi, Ito, Nishii, Taguchi, Yasui, Takao and Hataji.)

Background: Recent reports have indicated that the objective response rate (ORR) and progression-free survival (PFS) cannot serve as surrogates for predicting overall survival (OS) in immune checkpoint inhibitor (ICI) trials. We performed a trial-based correlative analysis to evaluate conventional endpoints as surrogates for predicting OS in ICI-treated non-small cell lung cancer (NSCLC) patients., Methods: A systematic electronic literature search for randomized clinical trials using ICI monotherapies for NSCLC revealed 7 trials. The correlative analysis to clarify the correlations among clinical outcomes used a weighted Spearman rank correlation coefficient (wS), weighted Pearson correlation coefficient (wP), and weighted linear regression model (wL) in all patients and patients with high PD-L1 expression., Results: The correlative analysis of the total population revealed that the odds ratio of the ORR (OR-ORR) and the hazard ratio of OS (HR-OS) were strongly correlated with the hazard ratio of PFS (HR-PFS) (R for wP and wS, R 2 for wL; -0.869, -0.968, 0.756 between OR-ORR and HR-PFS; 0.923, 0.959, 0.851 between HR-PFS and HR-OS). The strongest correlation was observed between one-year overall survival (1y-OS) and the HR-OS (R for wP and wS, R 2 for wL; 0.985, 1.000, R 2 : 0.968). In those with high PD-L1 expression, the ORR and PFS were strongly associated with OS (R 2 : 0.842 between ORR and OS; 0.771 between PFS and OS)., Conclusions: The OR-ORR and HR-PFS could serve as surrogate endpoints for predicting the HR-OS in randomized trials using ICIs for NSCLC, while the ORR and PFS could be useful endpoints for predicting OS in trials with patient selection based on high PD-L1 expression., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Bronchial occlusion with endobronchial Watanabe spigots (EWSs) can be an essential therapeutic measure for treating massive hemoptysis in intensive care patients when no other conventional options are available. A 68-year-old-man on mechanical ventilation and extracorporeal circulation after cardiovascular surgery presented massive hemoptysis. He was deemed unfit for bronchial artery embolization (BAE) and surgery while in the intensive care setting; thus, bronchial occlusion was performed using EWSs. His hemoptysis ceased, and he was successfully weaned from mechanical ventilation and extracorporeal circulation. Bronchial occlusion by EWSs may be considered an optimal, and at times, definitive treatment for obtaining hemostasis in these situations.

Background: The clinical benefit of liquid biopsy for unselected patients at initial diagnosis has thus far been unclear. We aimed to evaluate the utility of liquid biopsy at initial diagnosis, as well as the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) based on liquid biopsy results in clinical practice, using the improved peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp method., Patients and Methods: We routinely performed liquid biopsy using the improved PNA-LNA PCR clamp method for all patients diagnosed with non-small-cell lung cancer (NSCLC) between June 2015 and October 2016. We retrospectively evaluated the reliability of liquid biopsy based either on clinical stage or between sensitizing EGFR mutation and T790M mutation, and the clinical benefit of EGFR-TKI based on the liquid biopsy results in practice., Results: A total of 244 patients underwent liquid biopsies, with 168 patients tested at diagnosis and 22 tested for T790M after pretreatment of EGFR-TKI. For detecting a sensitizing EGFR mutation, the sensitivity, specificity, positive predictive value, and negative predictive value were 72.7%, 100%, 100%, and 93.7% in the group with advanced-stage NSCLC and 0, 100%, not evaluable, and 70.5% in the group with early-stage NSCLC. The positive predictive value and negative predictive value for T790M were 33.3% and 55.6%, respectively. Fourteen patients in the liquid-positive group and 16 patients in the tissue-positive group received EGFR-TKI. The objective response rates of first- and second-generation EGFR-TKI for the liquid-positive and tissue-positive groups were 90.0% and 90.9%, respectively. There was no significant difference in median progression-free survival between the liquid-positive and tissue-positive groups (P = .839)., Conclusion: Patients with early-stage NSCLC should not be candidates for this liquid biopsy method. We recommend tissue biopsy as the preferred initial method of molecular analysis, with the exception of patients who are T790M positive or patients who are unable to tolerate invasive biopsy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Combined therapy with tiotropium and olodaterol notably improves parameters of lung function and quality of life in patients with chronic obstructive pulmonary disease (COPD) compared to mono-components; however, its effect on physical activity is unknown. The present study evaluated whether combination therapy affects daily physical performance in patients with COPD under a smart watch-based encouragement program. This was a non-blinded clinical trial with no randomization or placebo control. A total of 20 patients with COPD were enrolled in the present study. The patients carried an accelerometer for 4 weeks; they received no therapy during the first 2 weeks but they were treated with combined tiotropium and olodaterol under a smart watch-based encouragement program for the last 2 weeks. The pulmonary function test, COPD assessment test, 6-min walk distance and parameters of physical activity were significantly improved (P<0.05) by combination therapy under smart watch-based coaching compared with values prior to treatment. To the best of our knowledge, the present study for the first time provides evidence that smart watch-based coaching in combination with tiotropium and olodaterol may improve daily physical activity in chronic obstructive pulmonary disease.

Introduction: We investigated whether adding ultrafine (nano-scale) oxygen-carrying bubbles to water concurrently with dissolved carbon-dioxide (CO2) could result in safe, long-duration anesthesia for fish., Results: To confirm the lethal effects of CO2 alone, fishes were anesthetized with dissolved CO2 in 20°C seawater. Within 30 minutes, all fishes, regardless of species, died suddenly due to CO2-induced narcosis, even when the water was saturated with oxygen. Death was attributed to respiration failure caused by hypoxemia. When ultrafine oxygen-carrying bubbles were supplied along with dissolved CO2, five chicken grunts were able to remain anesthetized for 22 hours and awoke normally within 2-3 hours after cessation of anesthesia., Conclusions: The high internal pressures and oxygen levels of the ultrafine bubbles enabled efficient oxygen diffusion across the branchia and permitted the organismal oxygen demands of individual anesthetized fish to be met. Thus, we demonstrated a method for safe, long-duration carbon dioxide anesthesia in living fish under normal water temperatures.

Atopic dermatitis (AD) is a refractory and recurrent inflammatory skin disease. Various factors including heredity, environmental agent, innate and acquired immunity, and skin barrier function participate in the pathogenesis of AD. T -helper (Th) 2-dominant immunological milieu has been suggested in the acute phase of AD. Antigen 85B (Ag85B) is a 30-kDa secretory protein well conserved in Mycobacterium species. Ag85B has strong Th1-type cytokine inducing activity, and is expected to ameliorate Th2 condition in allergic disease. To perform Ag85B function in vivo, effective and less invasive vaccination method is required. Recently, we have established a novel functional virus vector; recombinant human parainfluenza type 2 virus vector (rhPIV2): highly expressive, replication-deficient, and very low-pathogenic vector. In this study, we investigated the efficacy of rhPIV2 engineered to express Ag85B (rhPIV2/Ag85B) in a mouse AD model induced by repeated oxazolone (OX) challenge. Ear swelling, dermal cell infiltrations and serum IgE level were significantly suppressed in the rhPIV2/Ag85B treated mouse group accompanied with elevated IFN-γ and IL-10 mRNA expressions, and suppressed IL-4, TNF-α and MIP-2 mRNA expressions. The treated mice showed no clinical symptom of croup or systemic adverse reactions. The respiratory tract epithelium captured rhPIV2 effectively without remarkable cytotoxic effects. These results suggested that rhPIV2/Ag85B might be a potent therapeutic tool to control allergic disorders.