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Previous research on haptic search using sandpaper with different roughness levels as a target and distractors showed that rough sandpaper among fine “pops out” and can be searched for in a shorter time than when the roles of the target and distractors are reversed. However, it is not clear whether the same search asymmetry occurs with differences in the shapes of tactile symbols on capsule paper. To explore this possibility, we conducted a haptic search experiment using circles with or without a dot on capsule paper as a target and distractors, which are often used as point symbols in tactile maps for the blind. Contrary to our expectations, haptic search asymmetry did not occur between these two tactile symbols. Regardless of target type, the search times increased in proportion to the number of items (distractors plus target), as participants tended to adopt serial search strategy in which they placed their index or middle finger on the tactile symbol to distinguish it every time they found a new one. The ratio of the search times for target-absent to target-present trials is precise alignment with the occurrence rate of repetitive search trials.

Insufficient evidence has been accumulated regarding associations of heated tobacco products (HTPs) use with coronavirus infection and severity of coronavirus disease 2019 (COVID-19), an ongoing pandemic. We conducted a cross-sectional study using data from an internet questionnaire administered in February 2022 to 30,130 individuals from the general Japanese population (age range, 16–81 years). Single users of HTPs and dual users of combustible cigarettes and HTPs comprised 5.2% and 7.3% of respondents, and 6.7% and 38.0% of those infected (n = 1117). Approximately 70% of infected dual users experienced severe disease. Single users of HTPs and dual users were more likely to be infected with coronavirus than never-users (adjusted odds ratio [aOR] = 1.65/4.66; 95% confidence interval [CI] 1.26–2.15/3.89–5.58). Regarding severity, former and current tobacco users (former/combustible cigarettes/HTPs: aOR = 1.88/3.17/1.90; 95%CI 1.11–3.19/1.77–5.67/1.01–3.59) were more likely to be administered oxygen than never-users, and dual users required oxygen administration the most (aOR = 4.15, 95%CI 2.70–6.36). Use of HTPs may increase risks of coronavirus infection and severe COVID-19. Our results provide an opportunity to consider the safety of tobacco products use, including HTPs, during the COVID-19 pandemic.

Multiple reports have identified smoking as a risk factor for long COVID; however, few have distinguished among tobacco product types. We conducted a cross-sectional study using data from an internet-based survey administered in February 2023 to examine the association between 12 persistent symptoms and smoking status in participants with a history of COVID-19. A total of 28,250 participants were included, of whom 5,068 had a history of COVID-19. Among current tobacco users with a history of COVID-19, the odds ratios for persistent symptoms were significantly elevated for four symptoms—arthralgia, chest pain, dyspnea, and dysosmia—compared to never smokers. For subgroup analysis, current tobacco users were categorized into three groups: combustible cigarette (CC), heated tobacco product (HTP), and dual users. Among dual users, the odds ratios were significantly elevated for five symptoms: arthralgia, chest pain, dyspnea, dysgeusia, and dysosmia. CC users showed significantly higher odds for chest pain, dyspnea, and fatigue, while HTP users for dyspnea and sexual dysfunction. Smoking in individuals with a history of COVID-19 associates the prevalence of persistent symptoms, and its impact may vary by smoking type. Separately analyzing smoking subgroups allows for a more accurate understanding of the relationship between persistent symptoms and smoking behavior.

It is unclear whether tumor vascular endothelial growth factor receptor 2 expression affects the therapeutic efficacy of immune‐checkpoint inhibitors and antiangiogenic agents. This retrospective, multicenter study included patients with advanced non–small cell lung cancer who were treated with immune‐checkpoint inhibitors. We constructed tissue microarrays and performed immunohistochemistry with an anti‐vascular endothelial growth factor receptor 2 antibody. We analyzed immune and tumor cell staining separately in order to determine their correlation with the objective response rate, progression‐free survival, and overall survival in patients receiving immune‐checkpoint inhibitors. Of 364 patients, 37 (10%) expressed vascular endothelial growth factor receptor 2 in immune cells and 165 (45%) in tumor cells. The objective response rate, progression‐free survival, and overall survival were significantly worse in patients treated with immune checkpoint inhibitor monotherapy who expressed vascular endothelial growth factor receptor 2 in immune cells than those who did not (10% vs 30%, p = 0.028; median = 2.2 vs 3.6 months, p = 0.012; median = 7.9 vs 17.0 months, p = 0.049, respectively), while there was no significant difference based on tumor cell expression (24% vs 30%, p = 0.33; median = 3.1 vs 3.5 months, p = 0.55; median = 13.6 vs 16.8 months, p = 0.31). There was no significant difference in overall survival between patients treated with and without antiangiogenic agents in any treatment period based on vascular endothelial growth factor receptor 2 expression. Immune checkpoint inhibitor efficacy was limited in patients expressing vascular endothelial growth factor receptor 2 in immune cells. Vascular endothelial growth factor receptor 2 expression in non‐small cell lung cancer tissue, especially in immune cells, has a strong negative association with immune‐checkpoint inhibitor (ICI) efficacy. However, such a negative association was observed only in ICI monotherapy and not in ICI combination therapy with cytotoxic chemotherapy.

Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is a key cellular defense mechanism against oxidative stress. Recent studies have shown that astaxanthin protects against oxidative stress via Nrf2. In this study, we investigated the emphysema suppression effect of astaxanthin via Nrf2 in mice. Mice were divided into four groups: control, smoking, astaxanthin, and astaxanthin + smoking. The mice in the smoking and astaxanthin + smoking groups were exposed to cigarette smoke for 12 weeks, and the mice in the astaxanthin and astaxanthin + smoking groups were fed a diet containing astaxanthin. Significantly increased expression levels of Nrf2 and its target gene, heme oxygenase-1 (HO-1), were found in the lung homogenates of astaxanthin-fed mice. The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) was significantly decreased, and emphysema was significantly suppressed. In conclusion, astaxanthin protects against oxidative stress via Nrf2 and ameliorates cigarette smoke-induced emphysema. Therapy with astaxanthin directed toward activating the Nrf2 pathway has the potential to be a novel preventive and therapeutic strategy for COPD.

We retrospectively investigated the impact of the tumor microenvironment (TME) on the efficacy of epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs) as first‐line treatment in 70 patients with advanced EGFR‐mutant non‐small cell lung cancer and who were seen at Osaka City University Hospital (Osaka, Japan) between August 2013 and December 2017. Using immunohistochemical staining with 28‐8 and D7U8C Abs, the tumor proportion score was assessed for programmed cell death‐1 ligand‐1 (PD‐L1), as high (50% or more) or low (less than 50%), and ligand‐2 (PD‐L2) expression, respectively. The extent of CD8+ tumor‐infiltrating lymphocytes was evaluated on a scale of 0‐3, with 0‐1 as low and 2‐3 as high. The TME of the 52 evaluable pretreatment specimens was categorized into 4 subtypes, according to the respective PD‐L1 tumor proportion and CD8+ scores, as follows: (a) high/high (13.5%, n = 7); (b) low/low (42.3%, n = 22); (c) high/low (17.3%, n = 9); and (d) low/high (26.9%, n = 14). Expression of PD‐L2 was significantly the highest in type 1 (57.1% vs 4.5% vs 11.1% vs 7.1%, respectively; P = .0090). Response rate was significantly the lowest in type 1 (14.3% vs 81.8% vs 66.7% vs 78.6%, respectively; P = .0085). Progression‐free survival was the shortest in type 1 and the longest in type 4 (median, 2.4 vs 11.3 vs 8.4 vs 17.5 months, respectively; P = .00000077). The efficacy of EGFR‐TKIs differed according to the TME, and the phenotype with high PD‐L1 and CD8+ expression might be the subset that would poorly benefit from such treatment. We assessed the impact of the tumor microenvironment (TME) based on tumor programmed cell death‐1 ligand‐1 (PD‐L1) expression and CD8+ tumor‐infiltrating lymphocytes on the efficacy of epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) in patients with EGFR‐mutant non‐small cell lung cancer. The TME was categorized into 4 subtypes and the efficacy of EGFR‐TKIs differed according to the TME. The PD‐L1 high/CD8+ high phenotype might be the subset that would poorly benefit from EGFR‐TKI treatment.

PurposeKrebs von den Lungen-6 (KL-6) functions as a tumor marker, as well as a diagnostic tool for interstitial pneumonia (IP). However, the significance of KL-6 in the immune-checkpoint inhibitor (ICI) treatment of non-small cell lung cancer (NSCLC), especially in patients without IP, is unknown.MethodsThis multicenter, retrospective study, which included patients with advanced NSCLC who received ICI therapy, analyzed the association between serum KL-6 values and ICI efficacy and the association between serum KL-6 values and ICI-induced interstitial lung disease (ILD) occurrence, focusing primarily on patients without IP.ResultsIn total, 322 patients had available KL-6 values before ICI therapy. Among 202 patients without IP who received ICI monotherapy, the high-KL-6 group (≥ 500 U/mL) showed significantly shorter progression-free survival (PFS) and overall survival (OS) than the low-KL-6 group (< 500 U/mL) (median: 2.1 vs. 3.6 months, p = 0.048; median: 9.2 vs. 14.5 months, p = 0.035). There was no significant difference in response rate between the KL-6 high and low groups (19% vs. 29%, p = 0.14). In the multivariate analysis, high KL-6 was a significant predictor of poor PFS (hazard ratio [HR], 1.52; 95% confidence interval [CI] 1.10–2.11, p = 0.012) and OS (HR, 1.51; 95% CI 1.07 − 2.13, p = 0.019) for patients treated with ICI monotherapy. There was no significant difference in the occurrence rate of ILD between the high KL-6 and low KL-6 groups in patients with (20% vs. 15%, p = 1.00) or without IP (12% vs. 12%, p = 1.00).ConclusionIn ICI monotherapy for NSCLC without IP, elevated serum KL-6 levels were associated with poorer outcomes.

Epicardial connections provided the anatomical substrate for the biatrial reentry circuit. The connections between the right atrium and right pulmonary vein were called “intercaval bundle,” and there are few reports of atrial flutter related to this bundle. We present a case of a biatrial tachycardia, involving the intercaval bundle.

There is no real-world data in an Asian population to investigate the difference between the outcome of immune-checkpoint inhibitor (ICI) monotherapy and combination therapy for non-small cell lung cancer (NSCLC) based on smoking status. In this study, we investigated the correlation between smoking status and the efficacy of ICI therapy for NSCLC patients. This multicentre retrospective study enrolled patients with recurrent or metastatic NSCLC who were treated using ICI therapy between December 2015 and July 2020. We analysed the objective response rate (ORR) of patients who received ICI monotherapy or combination therapy, based on smoking status using Fisher's exact test, and progression-free survival (PFS) and overall survival (OS) based on smoking status using the Kaplan-Meier method, the log-rank test, and Cox proportional hazards model. A total of 487 patients were included in the study. In the ICI monotherapy group, non-smokers showed significantly lower ORR and shorter PFS and OS than smokers (10% vs. 26%, p=0.002; median: 1.8 vs. 3.8 months, p<0.001; median: 8.0 vs. 15.4 months, p=0.026). In the ICI combination therapy group, non-smokers showed significantly longer OS than smokers (median: not reached vs. 26.3 months, p=0.045), and there was no significant difference in ORR and PFS between non-smokers and smokers (63% vs. 51%, p=0.43; median: 10.2 vs. 9.2 months, p=0.81). In the multivariate analysis of patients who received ICI combination therapy, the \"non-smoker\" status was not significantly associated with PFS [hazard ratio (HR)=1.31; 95% confidence interval (CI)=0.70-2.45, p=0.40] and OS (HR=0.40; 95% CI=0.14-1.13, p=0.083). Non-smokers showed worse outcomes than smokers with ICI monotherapy, but not with ICI combination therapy.

Abstract Background: Transbronchial cryobiopsy enables high-quality sample collection around the probe tip. Meanwhile, existing cryoprobes have less flexibility and a higher risk of bleeding. The ultrathin cryoprobe with a 1.1-mm diameter addresses these problems and allows specimens to be directly retrieved through the working channel of a thin bronchoscope. Objective: This study evaluated the diagnostic utility and safety of non-intubated cryobiopsy using an ultrathin cryoprobe added to conventional biopsy for diagnosing peripheral pulmonary lesions (PPLs). Methods: The data of patients who underwent conventional biopsy followed by non-intubated cryobiopsy to retrieve specimens through the thin bronchoscope’s working channel for diagnosing PPLs at Osaka Metropolitan University Hospital from July 2021 to June 2022 were retrospectively collected. They were analyzed to evaluate the diagnostic utility and safety of adding non-intubated cryobiopsy to conventional biopsy for PPLs. The characteristics of PPLs that obtain additional diagnostic benefits from cryobiopsy over conventional biopsy were also investigated. Results: The analysis included 113 patients. The diagnostic yields of conventional biopsy and non-intubated cryobiopsy were 70.8% and 82.3%, respectively (p = 0.009). The total diagnostic yield was 85.8%, higher than conventional biopsy alone (p < 0.001). Although one moderate bleeding occurred, no severe complications developed. The additional diagnostic benefits of non-intubated cryobiopsy over conventional biopsy were demonstrated when the radial endobronchial ultrasound (R-EBUS) showed “adjacent to” (60.3% vs. 82.8%, p = 0.017). Conclusions: Non-intubated cryobiopsy using an ultrathin cryoprobe has high diagnostic utility and safety for diagnosing PPLs, with additional diagnostic benefits over conventional biopsy depending on the R-EBUS image.