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Background: Malignant pleural effusion (MPE) remains a negative prognostic factor in non-small cell lung cancer (NSCLC), even after the emergence of immune checkpoint inhibitors. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of MPE. Bevacizumab, a humanized monoclonal antibody against VEGF, is a key agent for patients who develop MPE. However, it is unclear whether MPE is a poor prognostic factor in patients with advanced non-squamous NSCLC receiving treatment with the atezolizumab plus bevacizumab, carboplatin, and paclitaxel (ABCP) regimen. Moreover, the effect of ABCP on MPE control is unknown. This study aimed to elucidate the efficacy and safety of ABCP for non-squamous NSCLC patients with MPE., Methods: We retrospectively analyzed consecutive patients with advanced non-squamous NSCLC who received treatment with ABCP (January 2019-September 2023). Patients were divided into two groups (non-MPE and MPE), and treatment outcomes were compared. In the MPE group, treatment efficacy for MPE control and toxicity were evaluated., Results: Of the 46 patients enrolled, 17 and 29 were included in the non-MPE and MPE groups, respectively. The objective response and disease control rates were not significantly different between the non-MPE and MPE groups (76.5% vs. 51.7%, P=0.13; 88.2% vs. 82.8%, P>0.99; respectively). Similarly, the median progression-free survival and median overall survival were not significantly different (9.9 vs. 10.1 months, P=0.87; 16.0 vs. 19.9 months, P=0.87, respectively). In the MPE group, 25 patients (86.2%) achieved MPE control lasting >8 weeks from the initiation of treatment with ABCP; the median progression-free survival without an unequivocal increase in MPE was 15.0 months. The incidence rates of grade ≥3 non-immune- and immune-related adverse events were 83% and 17%, respectively. There was no treatment-related death., Conclusions: The ABCP regimen may be a promising treatment option for non-squamous NSCLC patients with MPE., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-347/coif). K.H. reports personal fees from AstraZeneca, MSD, Kyorin Pharmaceutical, Chugai Pharmaceutical, and Daiichi-Sankyo, outside the submitted work. M.S. reports grants from Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, Nippon Kayaku, and Kyowa Hakko Kirin; and personal fees from AstraZeneca, MSD, Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly, Ono Pharmaceutical, Bristol-Myers Squibb, Nippon Boehringer Ingelheim, Pfizer, Novartis, Takeda Pharmaceutical, Kyowa Hakko Kirin, Nippon Kayaku, Daiichi-Sankyo, Merck Biopharma, and Amgen, outside the submitted work. T.H. reports grants from Chugai Pharmaceutical, Nippon Boehringer Ingelheim, and Taiho Pharmaceutical; and personal fees from Chugai Pharmaceutical, AstraZeneca, MSD, Bristol-Myers Squibb, Nippon Boehringer Ingelheim, Eli Lilly, Taiho Pharmaceutical, Daiichi-Sankyo, Takeda Pharmaceutical, Pfizer, and Novartis, outside the submitted work. The other author has no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Purpose: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is the standard treatment for patients with non-small cell lung cancer harboring EGFR mutations. Although the frequency of osimertinib-induced interstitial lung disease (osi-ILD) is high, the optimal cancer treatment after osi-ILD has not been established. This time, we focused on the safety and efficacy of gefitinib following osi-ILD., Case Presentation: We experienced six cases (five women and one man; median age: 74 years) in which gefitinib was administered after osi-ILD. All six cases had grade 2 or higher osi-ILD and required steroid treatment. The computed tomography imaging pattern of osi-ILD revealed organizing pneumonia in three cases, diffuse alveolar damage in two cases, and hypersensitivity pneumonia in one case. Eastern Cooperative Oncology Group performance status was 1 in four cases, 2 in one case, and 3 in one case. EGFR mutation status was exon 19 deletion in two cases and exon 21 L858R in four cases. Only one patient experienced recurrence of ILD after receiving gefitinib. The best response to gefitinib was partial response in two cases and stable disease in three cases; one case was not evaluable. The median progression-free survival after treatment with gefitinib was 190 days (95% confidence interval: 33-328)., Conclusion: The treatment with gefitinib after the development of osi-ILD was safe and effective. Gefitinib may be a promising option for patients who recovered from severe osi-ILD., Competing Interests: K. Hisakane reports receiving personal fees from AstraZeneca, MSD, Kyorin Pharmaceutical, Chugai Pharmaceutical, and Daiichi-Sankyo, outside the submitted work. M. Seike reports receiving grants from Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, Nippon Kayaku, and Kyowa Hakko Kirin; and personal fees from AstraZeneca, MSD, Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly, Ono Pharmaceutical, Bristol-Myers Squibb, Nippon Boehringer Ingelheim, Pfizer, Novartis, Takeda Pharmaceutical, Kyowa Hakko Kirin, Nippon Kayaku, Daiichi-Sankyo, Merck Biopharma, and Amgen, outside the submitted work. T. Hirose reports receiving grants from Chugai Pharmaceutical, Nippon Boehringer Ingelheim, and Taiho Pharmaceutical; and personal fees from Chugai Pharmaceutical, AstraZeneca, MSD, Bristol-Myers Squibb, Nippon Boehringer Ingelheim, Eli Lilly, Taiho Pharmaceutical, Daiichi-Sankyo, Takeda Pharmaceutical, Pfizer, and Novartis, outside the submitted work. The remaining authors have no conflicts of interest to declare for this work., (© 2024 Shimbu et al.)

In pulmonary hypertension (PH) associated with chronic lung disease (CLD), identifying patients who would benefit from pulmonary vasodilators is a significant clinical challenge because the presence of PH is associated with poorer survival. This study evaluated the severity of pulmonary circulation impairment in patients with CLD-PH using pulmonary perfusion single-photon emission computed tomography/computed tomography (SPECT/CT). This single-center, observational study enrolled patients with CLD-PH who had a mean pulmonary arterial pressure (PAP) ≥ 25 mmHg, as confirmed by right heart catheterization. The primary outcome was to measure the percentage of pulmonary perfusion defect (%PPD), calculated by dividing the perfusion defect volume from perfusion SPECT images by the lung volume from CT scan images. The secondary outcome was to assess the correlation between %PPD and baseline characteristics. The median %PPD was 52.4% (interquartile range, 42.5%-72.3%) in 22 patients. In multivariate linear regression analysis, both forced vital capacity ( β  = 0.58, p  = 0.008) and mean PAP ( β  = 0.68, p  = 0.001) were significantly correlated with %PPD. In conclusion, significant correlation between mean PAP and %PPD in patients with CLD-PH was observed. This noninvasive assessment of %PPD may be useful for evaluating the severity of pulmonary circulation impairment in CLD-PH., Competing Interests: Hiroshi Kimura worked in an endowment department supported by an unrestricted grant to Nippon Medical School from Actelion Pharmaceuticals Japan. The remaining authors declare no conflict of interest., (© 2024 The Author(s). Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Diazinon is an organophosphorus (OP) insecticides used in agriculture, home gardening and indoor pest control in Japan. It can activate macrophages and induce pro-inflammatory responses and has been reported to cause airway hyper-reactivity, suggesting the possibility of asthma exacerbation from exposure to OP insecticides. Despite the correlation between insecticide use and the pathogenesis of allergic diseases, there have been no reports on the effects of diazinon on mast cell function. Therefore, in this study, we investigated the effects of diazinon on mast cell function in rat basophilic leukemia (RBL)-2H3 cells. Surprisingly, we found that diazinon inhibited mast cell activation, although the degree of inhibition varied with concentration. Diazinon induced reactive oxygen species (ROS) generation and HO-1 expression at a concentration of 150 µM without affecting cell viability. Diazinon inhibited A23187-mediated degranulation and Tnf and Il4 expression in RBL-2H3 cells but did not affect calcium influx. Suppression of degranulation by diazinon was reversed when the culture supernatant was removed. As a signaling event downstream of calcium influx, diazinon inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) induced by A23187, whereas the phosphorylation of p38 had little effect. IgE cross-linking-mediated degranulation as well as the induction of Tnf and IL4 expression was significantly inhibited by diazinon, while diazinon had little effect on calcium influx. In conclusion, diazinon inhibited mast cell activation, including degranulation and cytokine expression. When evaluating the in vivo effects of diazinon, its potential to inhibit mast cell activation should be considered in the pathophysiology and development of allergic diseases in terms of basic and clinical aspects, respectively, although the effect of diazinon varies depending on the cell type., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sarcoidosis is a systemic granulomatous disease; however, the incidence of bone sarcoidosis is relatively rare. The short tubular bones of the hands and feet are most frequently affected, while the vertebrae and the pelvic bones are rarely involved. We hereby report a rare case of multiple bone sarcoidosis involving the vertebrae and pelvic bones, evaluated before and after steroid therapy using two different imaging modalities: bone scintigraphy and A 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT). FDG-PET/CT is effective for detecting bone lesions; however, whole-body imaging is recommended to detect the short tubular bones of the hands and feet, which are most frequently affected., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)