Introduction: This study aimed to evaluate the real-world clinical outcomes of pembrolizumab monotherapy in patients with advanced NSCLC with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of 1% to 49%. Methods: A multicenter retrospective analysis was conducted for outcomes of 114 patients with stages II to IV or recurrent NSCLC and PD-L1 TPS of 1% to 49%, who received first-line pembrolizumab monotherapy. Results: The median progression-free survival (PFS) was 5.6 months, with 6-month and 60-month PFS rates of 47.4% and 5.1%, respectively. The median overall survival (OS) was 15.8 months, with 24-month and 60-month OS rates of 34.8% and 17.0%, respectively. The objective response rate was 36.9%, and the disease control rate was 60.4%. Multivariate analysis identified liver metastasis as a significant negative prognostic factor for PFS, but a high neutrophil-to-lymphocyte ratio (NLR) revealed a trend toward worse PFS. Similarly, liver metastasis, high NLR, and poor performance status were significantly associated with worse OS. Grade more than or equal to 3 immune-related adverse events were observed in 20.2% of patients, with pneumonitis being the most common. Those with a history of interstitial lung disease had a higher incidence of severe pneumonitis than those without. Treatment discontinuation due to disease progression occurred in 65.8% of patients, whereas 23.7% discontinued due to adverse events. Conclusions: First-line pembrolizumab monotherapy demonstrated moderate efficacy and acceptable safety in patients with advanced NSCLC with PD-L1 TPS of 1% to 49%. Liver metastasis, high NLR, and poor performance status were identified as prognostic factors.
Purpose To determine the prevalence of apical scarring-which has recently also been referred to as pleuroparenchymal fibroelastosis (PPFE)-like lesions, a characteristic finding at chest CT in idiopathic PPFE-in apparently healthy individuals, to identify associated clinical features, and to evaluate their progression over time. Materials and Methods This retrospective study included individuals without underlying diseases known to cause PPFE, who underwent comprehensive health checkups including chest CT between April 2014 and March 2015 (cohort 1: n = 1737; cohort 2: n = 1126). Clinical features associated with the presence of apical scarring were analyzed using propensity score matching and logistic regression analysis. Furthermore, in a subset of individuals with available follow-up data, radiologic progression of apical scarring was evaluated over a 4-year period from baseline, and potential risk factors were evaluated using a logistic regression model. Results Among 2863 individuals (median age, 57 years [IQR, 49-65 years]; 2299 male), 158 (5.5%) had apical scarring, with prevalence rates of 1.6%, 3.9%, and 8.1% in individuals aged 20-39 years, 40-59 years, and 60 years and older, respectively. Older age and lower body mass index, body fat, and waist circumference were associated with apical scarring. These findings were consistent in both cohorts. Among the 158 individuals with apical scarring, at least 20 (12.7%) demonstrated radiologic progression over 4 years, which was more common in those with more extensive lesions at baseline (progression rate: grade 1 lesions, 19.2% vs grade 2 lesions, 66.7%; P = .006). Conclusion Among apparently healthy individuals, the prevalence of apical scarring increased with age, and its presence was associated with a lean body habitus. Radiologic progression was observed in some individuals. Keywords: CT, Thorax, Lung, Epidemiology, Apical Cap, Interstitial Lung Disease, PPFE, PPFE-like lesions, Pleuroparenchymal Fibroelastosis Supplemental material is available for this article. © RSNA, 2026.
The 2024 revised edition of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG 2024) is published by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine. This is the fourth revision since the first edition was published in 2012. The purpose of the guidelines is to assist healthcare providers in making appropriate decisions in the treatment of sepsis and septic shock, leading to improved patient outcomes. We aimed to create guidelines that are easy to understand and use for physicians who recognize sepsis and provide initial management, specialized physicians who take over the treatment, and multidisciplinary healthcare providers, including nurses, physical therapists, clinical engineers, and pharmacists. The J-SSCG 2024 covers the following nine areas: diagnosis of sepsis and source control, antimicrobial therapy, initial resuscitation, blood purification, disseminated intravascular coagulation, adjunctive therapy, post-intensive care syndrome, patient and family care, and pediatrics. In these areas, we extracted 78 important clinical issues. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 42 GRADE-based recommendations, 7 good practice statements, and 22 information-to-background questions were created as responses to clinical questions. We also described 12 future research questions.
This article translates the guidelines for the treatment of empyema established by the Japanese Association of Chest Surgery in 2023 from Japanese to English. These guidelines were developed by the Working Group on Guidelines for the Treatment of Empyema of our society, involving the establishment of clinical questions, conducting systematic reviews in accordance with the MINDS (Medical Information Distribution Service) Manual for Guideline Development 2020 version 3.0 and the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system, and determining the levels of recommendations. Furthermore, external evaluators provided assessments. Subsequently, the guidelines were finalized after receiving public comments from the members of the society. Even in the current era of advanced antibiotic therapy, empyema remains difficult to treat. However, the specific guideline for the treatment of empyema lacks in our country. Each institution is conducting clinical practices in its own way. Therefore, aiming to standardize the treatment of empyema, we have developed a practice guideline of empyema treatment. The pathophysiology of empyema is diverse, so empyema is classified into acute, chronic, and postoperative empyema. The recommended surgical treatment for each type of empyema is described, being categorized by the strength of recommendation, strength of evidence, and consensus rate.
PURPOSE:Rearranged during transfection (RET) aberrations represent a targetable oncogene in several tumor types, with RET inhibitors displaying marked efficacy. However, some patients with RET-aberrant cancer are insensitive to RET tyrosine kinase inhibitors (TKI). Recently, drug-tolerant mechanisms have attracted attention as targets for initial therapies to overcome drug resistance. The underlying mechanisms of drug-tolerant cell emergence treated with RET-TKIs derived from RET-aberrant cancer cells remain unknown. This study investigated the role of YAP-mediated HER3 signaling in the underlying mechanisms of adaptive resistance to RET-TKIs in RET-aberrant cancer cells. EXPERIMENTAL DESIGN:Four RET-aberrant cancer cell lines were used to assess sensitivity to the RET-TKIs selpercatinib and pralsetinib and to elucidate the molecular mechanisms underlying adaptive resistance using RNA sequencing, phospho-receptor tyrosine kinase antibody arrays, chromatin immunoprecipitation assay, and luciferase reporter assays. Clinical specimens from patients with RET fusion-positive lung cancer were analyzed for pretreatment YAP expression and correlated with treatment outcomes. RESULTS:In high YAP-expressing RET-aberrant cancer cells, YAP-mediated HER3 signaling activation maintained cell survival and induced the emergence of cells tolerant to the RET-TKIs selpercatinib and pralsetinib. The pan-ErBB inhibitor afatinib and YAP/tea domain inhibitors verteporfin and K-975 sensitized YAP-expressing RET-aberrant cancer cells to the RET-TKIs selpercatinib and pralsetinib. Pretreatment YAP expression in clinical specimens obtained from patients with RET fusion-positive lung cancer was associated with poor RET-TKI treatment outcomes. CONCLUSIONS:The YAP-HER3 axis is crucial for the survival and adaptive resistance of high YAP-expressing RET-aberrant cancer cells treated with RET-TKIs. Combining YAP/HER3 inhibition with RET-TKIs represents a highly potent strategy for initial treatment. See related commentary by Ortiz-Cuaran and Leonce, p. 958.
