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Introduction: Studies have shown the antitumor efficacy of immune checkpoint inhibitors (ICI) in patients with non‐small cell lung cancer (NSCLC) and brain metastases (BM). However, it is unclear whether the efficacy of ICI is similar between patients with and without BM. It is yet unclear whether the efficacy of ICI in patients with BM increases with higher levels of programmed cell death‐ligand 1 (PD‐L1) expression, as observed in patients without BM. Methods: We compared the outcomes of ICI treatment between patients with and without BM using a cohort containing 1741 prospectively enrolled patients with lung cancer. We investigated whether there were differences in the outcomes of ICI based on PD‐L1 expression levels between these patients. Results: We enrolled 240 patients with NSCLC with or without BM who were treated with ICI or both chemotherapy and ICI. There were no significant differences in overall survival (OS) between all patients with or without BM (p = 0.489). However, OS was significantly shorter in patients with BM than in those without in the PD‐L1 ≥ 50% group (16.5 M vs. 30.6 M, p = 0.003) but not in the PD‐L1 ≥ 1% or negative group. BM was an independent poor prognostic factor for OS (hazard ratio: [95% confidence interval], 2.045; [1.058–3.953], p = 0.033) in the PD‐L1 ≥ 50% group. Conclusion: Our study indicated that the outcomes of patients with or without BM treated with ICI were not significantly different. The efficacy of ICI in patients with PD‐L1 expression ≥50% would be lower in patients with BM than in those without. [ABSTRACT FROM AUTHOR]

Introduction: During an oral food challenge (OFC), there is a risk of adverse reactions, including anaphylaxis. Therefore, the physician should carefully conduct the OFC. This study aimed to evaluate the OFC results in individuals with low levels of egg white (EW)- and ovomucoid (OVM)-specific immunoglobulin E (sIgE) and the safety of a hen's egg (HE) OFC in these individuals. Methods: A total of 2,058 individuals with low EW- or OVM-sIgE underwent HE-OFC at two institutions in Kumamoto prefecture, located in the western area of Japan, between January 1, 2017, and December 31, 2021, within 1 year of recorded sIgE measurements. The ImmunoCAP systems were used to measure sIgEs. The HE-OFC test was performed according to the 2017 Food Allergy Guidelines in an open and unblinded method. Results: Five hundred and one individuals (24.3%) had low EW-sIgE levels (class 2 or lower), and 926 (45.0%) had low OVM-sIgE levels (class 2 or lower). Individuals with low EW-sIgE had lower total IgE and OVM-sIgE than did those with high EW-sIgE (greater than class 2). Those with low OVM-sIgE had lower total IgE and EW-sIgE than did those with high OVM-sIgE (greater than class 2). Among the individuals with low EW-sIgE, 86.4% (433/501 cases) passed the OFC without symptoms. Among the individuals with low OVF-sIgE, 82.6% (765/926 cases) passed the OFC without symptoms. Conclusion: More than 80% of individuals with suspected IgE-dependent HE allergy and low levels of EW- or OVM-specific IgE were able to consume at least a small amount of HE. As the OFC results are independent of the loading dose in cases with low EW- or OVM-sIgE, a medium-dose HE-OFC may be performed safely in individuals with no history of anaphylaxis. [ABSTRACT FROM AUTHOR]

Background Japanese encephalitis (JE) is the leading cause of viral encephalitis with high mortality and morbidity in Asia. In Japan, however, the active recommendation of JE vaccine was retracted in 2005 because of the potential risk of acute disseminated encephalomyelitis. We aimed to determine the recent incidence of childhood-onset JE after the domestic change of vaccination policy in Japan, and to analyze the clinical features of affected children. Methods A retrospective nationwide survey was conducted for pediatric patients with JE in Japan from 1995 to 2015. The national surveillance system was used to identify the pediatric patients with JE. Follow-up questionnaires were sent to analyze their clinical and neuroimaging profiles. Results Among a total of 109 patients registered to the national surveillance, 10 (9%) were less than age 15 years. The annual incidence rate of childhood-onset JE was higher during 2005–15 than that during 1995–2004 (4.3 × 10–3 vs 1.1 × 10–3 per 100000, respectively; P =.04). Endemic regions overlapped with prefectures that farmed pigs harboring antibodies against JE virus with high prevalence. Detailed clinical data were collected from 9 patients. None of them died, but 5 of 9 patients (56%) had neurological sequelae after recovery. One patient who was partially vaccinated with 2 doses of JE vaccine fully recovered from a coma. The age of 3 years or less was associated with unfavorable neurological prognosis. Conclusions Our data provide evidence for the importance and prophylactic effect of the JE vaccine in young children in the endemic area. [ABSTRACT FROM AUTHOR]

Introduction: Cow’s milk (CM) is one of the most common food allergens in Japan. The oral food challenge (OFC) of CM is important for the definite diagnosis of children with CM allergy, and it is recommended to be actively and safely performed in individuals with low CM-sIgE levels. This study aimed to investigate the safety of low-dose CM-OFC in individuals with low CM-sIgE levels and discuss the prognostic factors and appropriate approaches for assessing the starting doses of CM-OFC in these individuals. Methods: We retrospectively analyzed 6,929 OFC tests conducted between January 1, 2017, and December 31, 2021; of which, 1,390 were CM-OFC tests. The characteristics, OFC-positive rates, CM loading, and related factors were analyzed in 138 cases involving low CM-sIgE levels. Stepwise OFC tests were conducted according to the food allergies guidelines in Japan using an open and unblinded method. Results: Among 138 individuals with low CM-sIgE levels, 110 (79.7%) passed the OFC test without any symptoms. Among the cases with OFC-positive status, 50.0% (14/28) cases showed symptoms with low-dose OFC (30–105 mg CM protein). Moreover, complete CM elimination was associated with a significantly high OFC-positive rate, and 60.0% (12/20) of the cases involving complete CM elimination showed symptoms with low-dose OFC. Conclusion: Eighty percent of the patients with low CM-sIgE levels safely completed the OFC test. Nevertheless, careful observation is essential during low-dose OFC test in cases with low CM-sIgE levels, especially in the cases with complete elimination. The starting dose of the OFC test should be reevaluated, and modified using baked milk or a lower dose of CM to ensure safety and early outgrowth of CM allergy. [ABSTRACT FROM AUTHOR]

\nIntroduction: Stepwise oral food challenge (OFC) tests begin with low doses of allergens and progress to full doses. We previously reported the safety and efficacy of stepwise OFC for reintroducing hen eggs. In this study, we discuss its application for cow’s milk (CM) allergy. Methods: We included 927 children (median age, 3.2 years) who underwent CM-OFC between 2017 and 2021. The target challenge dose was classified as low (<10 mL), middle (≥10 mL but <100 mL), or full. When participants reacted to the low dose, they underwent a very low-dose OFC using baked milk or <1 mL of CM. Results: Positive reactions occurred in 210 cases (22.7%), including 69 anaphylactic reactions (7.4%). A lower target dose resulted in more positive OFC results (p < 0.001) and anaphylaxis (p = 0.001). The lower dose group included more children with complete elimination of CM (p < 0.001), with numerous histories of anaphylaxis induced by CM (p < 0.001), and higher levels of total IgE (p = 0.033) and CM-sIgE (p < 0.001). A multivariate analysis indicated that in the low-dose-OFC group, higher CM-sIgE levels (p = 0.034), younger age (p = 0.005), and complete elimination of CM (p = 0.002) were associated with positive OFC results. Conclusion: The stepwise OFC could reintroduce small amounts of CM, even in cases with high CM-sIgE levels or a history of anaphylaxis. Performing CM-OFC at younger ages, specifically from infancy, with very low doses, might facilitate the safe reintroduction of CM. Stepwise oral food challenge (OFC) tests begin with low doses of allergens, progressing to full doses. This is one of the strategies used to avoid anaphylactic reactions to the reintroduction of allergens. We previously reported the safety and efficacy of hen egg OFC. In this study, we discuss it for cow’s milk (CM) allergy. We included 927 children (median age, 3.2 years) who underwent CM-OFC between 2017 and 2021. The target challenge dose was classified as low (<10 mL), middle (≥10 mL but <100 mL), or full. When the participants reacted to low doses, they underwent very low-dose OFC using baked milk or <1 mL of CM. Positive reactions developed in 210 cases (22.7%), including 69 anaphylactic reactions (7.4%). A lower target dose resulted in more positive OFC results and anaphylaxis. Multivariate analysis indicated that only in low-dose OFCs, higher CM-specific IgE (CM-sIgE) levels, younger age, and complete CM elimination were associated with positive OFC results. Food ladders, an approach to reintroduce allergens, are becoming increasingly popular. Although we believe that OFC is a safer strategy to reintroduce CM to children with CM allergy, our CM-OFCs appeared to develop more anaphylactic reactions than milk ladders. The stepwise OFC reintroduced small amounts of CM, even in cases with high CM-sIgE levels or a history of anaphylaxis. Performing CM-OFC at a younger age, preferably from infancy, with very low doses, similar to milk ladders, may facilitate the safe reintroduction of CM. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are highly effective against EGFR-mutant non-small-cell lung carcinoma but can cause serious adverse events, such as interstitial lung disease (ILD). Treatment strategies for osimertinib-induced ILD are not well established. Cytotoxic anticancer drugs are considered first, although several cases of successful rechallenge with EGFR-TKIs have been reported. We herein report a 67-year-old woman with symptomatic osimertinib-induced ILD who was switched to afatinib and later rechallenged with osimertinib and corticosteroids. Neither treatment resulted in ILD relapse, suggesting that these may be viable treatment options when alternative treatments are limited.

Nitrogen-containing bisphosphonates (N-BPs), which are usually used for the treatment of advanced cancer with bone metastasis, occasionally cause fever following the first administration. However, it is unclear as to how the development of fever following the first administration of N-BP is associated with clinical outcome. The aim of the present study was to determine the prognostic value of the development of fever following the first administration of N-BP in advanced non-small cell lung cancer patients with bone metastases. The present study reviewed the data of 46 patients with advanced non-small cell lung cancer who were administered zoledronate (ZOL), an N-BP, for bone metastasis, between March 2009 and March 2011 in the Department of Medical Respirology at Tottori University Hospital. Clinicopathological factors were evaluated using univariate and multivariate analyses, and these factors were compared between the fever and non-fever groups. Of the 46 patients, 15 (32.6%) developed fever following the first administration of ZOL. No significant differences were observed in the clinicopathological characteristics between the two groups. The overall survival in the fever group was significantly longer compared with the non-fever group (median survival time: 33.4 vs. 15.7 months, P=0.04), and the development of fever following the first ZOL administration was independently associated with longer overall survival. The development of fever following the first ZOL administration was an independent prognostic factor in advanced non-small cell lung cancer patients with bone metastases. Thus, ZOL-associated fever may be a predictive factor for an undefined, survival-promoting effect of ZOL.

Background: Tocotrienols, members of the vitamin E family, exist in four different isoforms (α, β, γ and δ tocotrienol) that have can be protective against brain damage, as well as having anticancer effects in vivo and in vitro . We have shown that γ-tocotrienol inhibits human airway smooth muscle cell proliferation and migration induced by platelet-derived growth factor (PDGF)-BB by suppressing RhoA activation. In this study, we tested whether γ-tocotrienol modulates transforming growth factor (TGF) -β-induced induction of human airway smooth muscle (ASM) into a contractile phenotype and concomitant synthesis of extracellular matrix proteins., Methods: ASM cells were stimulated with TGF-β1 (2 ng/mL) for 48 hours and the effect of γ-tocotrienol (50 μM) on α-smooth muscle actin, fibronectin and collagen I expression was assessed using Western blotting. The signaling pathways involved in TGF-β1 stimulation were also investigated., Results: TGF-β1 increased α-smooth muscle actin, fibronectin and collagen Ⅰ abundance by 3- to 5-fold. This response was inhibited significantly by γ-tocotrienol. Furthermore, γ-tocotrienol suppressed RhoA activation, but did not affect Smad2 or Smad3 phosphorylation., Conclusion: These results indicate that γ-tocotrienol has potential for benefit in modulating on airway remodeling in asthma, likely via a mechanism involving the suppression of TGF-β activation of RhoA.