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Current evidence indicates that immune checkpoint inhibitors (ICIs) have a limited efficacy in patients with lung cancer harboring epidermal growth factor receptor (EGFR) mutations. However, there is a lack of data on the efficacy of ICIs after osimertinib treatment, and the predictors of ICI efficacy are unclear.We retrospectively assessed consecutive patients with EGFR-mutant NSCLC who received ICI-based therapy after osimertinib treatment at 10 institutions in Japan, between March 2016 and March 2021. Immunohistochemical staining was used to evaluate the expression of p53 and AXL. The deletions of exon 19 and the exon 21 L858R point mutation in EGFR were defined as common mutations; other mutations were defined as uncommon mutations.A total of 36 patients with advanced or recurrent EGFR-mutant NSCLC were analyzed. In multivariate analysis, p53 expression in tumors was an independent predictor of PFS after ICI-based therapy (p = 0.002). In patients with common EGFR mutations, high AXL expression was a predictor of shorter PFS and overall survival after ICI-based therapy (log-rank test; p = 0.04 and p = 0.02, respectively).The levels of p53 in pretreatment tumors may be a predictor of ICI-based therapy outcomes in patients with EGFR-mutant NSCLC after osimertinib treatment. High levels of AXL in tumors may also be a predictor of ICI-based therapy outcomes, specifically for patients with common EGFR mutations. Further prospective large-scale investigations on the predictors of ICI efficacy following osimertinib treatment are warranted.

International audience; ChEC91, a novel cell death-inducing effector protein from the fungal pathogen Colletotrichum higginsianum, causal agent of crucifer anthracnose disease, is described. Both transient expression of ChEC91 and infiltration of purified recombinant protein induced necrotic lesions in Nicotiana benthamiana leaves. The recombinant protein also induced electrolyte leakage and callose deposition in Arabidopsis thaliana leaf tissue and the expression of defence marker genes. Moreover, fungal mutants constitutively over-expressing ChEC91 in C. higginsianum were impaired in appressorial penetration on Brassica rapa cotyledons. These results suggest that inappropriate expression of ChEC91 might negatively affect the early stage of C. higginsianum infection by inducing plant defence responses. Protein domain deletion analysis showed that the C-terminal region of ChEC91 was necessary, but not sufficient, for activity in N. benthamiana. Homologous effector proteins cloned from C. gloeosporioides, Fusarium graminearum, and Pyricularia oryzae differed in their cell death-inducing activity, which appeared related to sequence variations in the C-terminal region of these proteins. Moreover, this region contained amino acid residues that were well conserved within Colletotrichum species. These results suggest that the amino acid residues in the C-terminal region may be important for inducing cell death in plants.

Growth morphology of carbon clusters deposited on different substrates were investigated by theoretical and experimental approach. For theoretical approach, molecular dynamics was employed to evaluate an adsorptive stability of different size of carbon clusters placed on different substrates. The adsorptive stability was estimated by the difference of total energy of supercell designed as carbon cluster placed on a certain crystal plane of substrate. Among the simulations of this study, carbon cluster flatly settled down on the surface of SrTiO$$_{3}$$ 3 (001). The result was experimentally verified with layer by layer growth of graphene by pulsed laser deposition in carbon dioxide atmosphere. The absorptive stability can be useful reference for screening substrate for any target material other than graphene.

[Purpose] To describe our newly developed Sedentary Behavior and Light-Intensity Physical Activity Questionnaire and examine its reliability and validity. [Participants and Methods] We identified and selected self-reported items through a literature review and interviews with 11 inactive individuals. Thirty-one individuals with lower limb prostheses and an expert panel assessed the content validity of the integrated items and identified 17 items. Patients who had undergone lower limb surgeries were regarded as inactive individuals, and 112 patients completed the questionnaire twice for test-retest reliability and wore an accelerometer for criterion validity. The ethics committee of Kyushu University approved this study (2019-126 and 2019-273). [Results] Item analysis was revised to the Sedentary Behavior and Light-Intensity Physical Activity Questionnaire-10 (six light-intensity physical activity and four sedentary behavior items) because of the floor effect. The test-retest correlation coefficient showed high reliability. Moderate to weak correlation coefficient was observed between the questionnaire and accelerometer (light-intensity physical activity: 0.43 and sedentary behavior: 0.20), and the Bland-Altman plots indicated no bias. [Conclusion] The Sedentary Behavior and Light-Intensity Physical Activity Questionnaire-10 had acceptable validity and reliability among inactive individuals and it could be used for studying light-intensity physical activity.

Background Over 40% Japanese patients with lung cancer are above 75 years of age. A specific strategy to treat such older patients is necessary because most trials exclude older patients with poor physical health. Herein, we aimed to identify predictive factors associated with overall survival (OS) in older patients by evaluating patient backgrounds and laboratory data before the start of treatment. Methods This multicenter retrospective medical chart review study was conducted at three Japanese institutions and involved patients aged 75 years and above with epidermal growth factor receptor (EGFR) mutation-negative advanced non-small cell lung cancer (NSCLC). Of the patients, 75 had received best supportive care (BSC) and 49 mono-chemotherapy or platinum-doublet chemotherapy, including immune checkpoint inhibitors (ICIs). OS after diagnosis was analyzed using the Kaplan-Meier survival analysis. Cox proportional hazard models, which included age, Eastern Cooperative Oncology Group performance status (ECOG PS), staging, serum albumin levels, and receipt of chemotherapy were analyzed. Results Age at diagnosis was not shown to be related to OS in patients receiving BSC. In patients aged 81 years and above, the chemotherapy group tended to have longer survival than did the BSC group, but there was no statistically significant difference in the median OS between the two groups due to the very small number of subjects (n: 30 vs. 12, median: 52 vs. 30 weeks, hazard ratio: 0.512, 95% confidence interval: 0.232-1.130, P=0.088). The patients' performance status and albumin levels at lung cancer diagnosis had the highest impact on OS in the BSC group. Conclusions Careful consideration should be given to the indications of chemotherapy for patients aged 81 years and above with wild-type EGFR advanced non-small lung cancer.

The Hospital for Special Surgery Hip Replacement Expectations Survey (HSS-THRES) is used in many countries to determine patient expectations before surgery. This study aimed to assess the reliability and validity of the Japanese version of HSS-THRES.A total of 134 patients scheduled for total hip arthroplasty (THA) underwent a self-administered preoperative survey questionnaire. Patient's expectation and quality of life (QOL) were measured using the Japanese version of HSS-THRES, overall expectations for THA, Oxford hip score (OHS), and EuroQol-5D (EQ-5D). Some patients completed the Japanese version of HSS-THRES and the overall expectations for THA after a ten-day interval. Cross-cultural adaptation was validated by an expert committee comprising health professionals, a methodologist, language experts, and orthopedic specialists. The internal consistency was evaluated by the Cronbach α coefficient. The test-retest reliability was examined using the intraclass coefficient correlation (ICC) and the Bland and Altman analysis. To test the construct validity, nine priori hypotheses were tested by correlation analysis between the Japanese version of HSS-THRES and two QOL scales, and by examining the association with demographic variables.A total of 116 patients completed four scales. Patients were predominantly female (75.9%), with an average age of 62.2 ± 11.7. In the cross-cultural adaptation, all patients responded to the questionnaire without problems. The Japanese version of HSS-THRES showed good internal consistency (Cronbach α: 0.9). ICC was 0.94 and Bland-Altman analysis indicated no bias. The correlation between Japanese HSS-THRES and overall expectations for THA was high (r = 0.67). Similarly, the correlation with the OHS was higher than that with EQ-5D. A total of 77.8% of the hypotheses were confirmed.The Japanese version of HSS-THRES showed good cultural acceptability, high reliability, and validity to evaluate preoperative expectations for THA patients.

Background / Regular physical activity (PA) is important for maintaining mental and physical health after liver transplantation (LT); however, the fluctuations in routine PA during COVID-19 and its putative impacts are currently unknown. This study examined the changes in PA during the COVID-19 pandemic and explored its association with fear and depression during the pandemic. / Material/Methods / This longitudinal study included 83 LT patients whose PA was measured using the short form of the International Physical Activity Questionnaire before and during COVID-19. Fear of COVID-19 was estimated based on previous studies, and depression was assessed using the Patient Health Questionnaire-9. Participants were also asked about important sources of information on COVID-19. PA was classified as inactive or active depending on the changes in PA, and logistic regression analyses with PA as a dependent variable were conducted to explore the associations among PA, depression, and fear of COVID-19. / Results / Moderate and high PA exhibited decreasing trends before and during the COVID-19 pandemic, especially in males. Fear of being infected with SARS-CoV-2, the virus that causes COVID-19, while shopping was significantly higher in females and was significantly independent of inactivity during the COVID-19 pandemic. Only 1 patient reported that their transplant center was their main source of information about COVID-19. Only 4.9% of the LT participants were depressed. / Conclusions / Our study results indicate the need to support the provision of accurate information about COVID-19 by health care professionals in transplant centers, especially for patients with low PA, to prevent PA decline in LT patients.

Purpose The primary objective of this study was to identify the potential predictors to assess impact of maintenance therapy after induction immunochemotherapy in the real-world setting of patients with advanced non-small cell lung cancer (NSCLC). Methods We retrospectively identified 152 patients with advanced NSCLC who received immunochemotherapy at eight hospitals in Japan between January 2019 to December 2019. Patients who received at least four cycles of induction immunochemotherapy and one cycle of maintenance therapy with immune-checkpoint inhibitors were included. We investigated the biomarkers for progression-free survival (PFS) for maintenance therapy after induction immunochemotherapy. Results Out of the 92 patients with advanced NSCLC included in the study, 42 received maintenance therapy with cytotoxic agents whereas 50 received maintenance therapy without cytotoxic agents. Among those who received maintenance therapy without cytotoxic agents, responders to prior immunochemotherapy had significantly longer PFS than non-responders (p = 0.004), except those with maintenance therapy with cytotoxic agents. In non-responders to prior immunochemotherapy, patients with maintenance therapy with cytotoxic agents had significantly longer PFS than those with maintenance therapy without cytotoxic agents (log-rank p = 0.007), whereas among responders to prior immunochemotherapy, there was no significant difference in PFS for different maintenance regimens (log-rank p = 0.31). Conclusions This retrospective study showed that response to prior immunochemotherapy was associated with clinical outcomes among patients with advanced NSCLC who received maintenance therapy.

Cancer cachexia is defined as a multifactorial syndrome that causes anorexia and an ongoing loss of skeletal muscle mass (with or without loss of fat mass). When patients got cachexia, the effectiveness and tolerance for anti-cancer therapy is reduced, leading to their poor prognosis. Although known as such disease, there had been no effective cure for cancer cachexia. Ghrelin is a peptide hormone that promotes appetite and improve cachexia. However, there is a limitation as a drug because its half-life is short and must be intravenous injected. Anamorelin is a first novel drug, an orally active, non- peptidic ghrelin mimetic and growth hormone secretagogue approved in Japan in January 2021. Like ghrelin, anamorelin also increases the appetite and lean body mass of patients with cancer cachexia. On the other hand, in clinical trials, there was no statistical significance for increasing the 6-minute walk test distance and recovering non-dominant hand grip strength. As for the functional recovery, a new program has been developed for non-pharmacotherapy with nutritional and exercise interventions. These 2 kinds of interventions will become effective anti-cachexia therapy. Research is also underway to produce anti-cachexia drugs other than anamorelin. Somes are already in their clinical trials. Anti-cachexia therapy will be a new option for treating advanced cancer.

Aim To evaluate the effects of an intensity display type accelerometer on diabetic patients' physical activity. Methods This was a two-arm, non-randomized controlled study. Both groups received information about the recommendation of 150 min/week moderate-to-vigorous physical activity (MVPA). The intervention group used an intensity display type accelerometer to monitor their physical activity intensity for 10 days at baseline and 3 months later. We compared intervention and control groups after 3 and 6 months. Primary outcomes were MVPA and number of steps over 7 days. Secondary outcomes were glycosylated hemoglobin (HbA1c), body mass index, and self-management. Results Of 62 participants, 30 and 32 were included in the intervention and control groups, respectively. Mean age in each group was 59.7 ± 10.8 and 58.8 ± 10.2 years, and mean HbA1c was 6.9 ± 0.9% and 6.9 ± 0.8%, respectively. There were no significant differences between the intervention and control groups at either time point, and no outcomes showed significant changes. In a subgroup analysis by physical activity intensity, MVPA of active individuals in the control group significantly decreased at 6 months from baseline. MVPA and number of steps among inactive individuals in the intervention group significantly increased at 6 months from baseline. Self-management of the intervention group showed a trend toward improvement, but HbA1c and body mass index showed no significant change. Conclusions Monitoring physical activity intensity led to increased MVPA of inactive patients and maintained MVPA of active patients with diabetes mellitus. This straightforward intervention could be applied in clinical practice.

The conventional skin color separation method suffers from the severe limitation that the input skin image must have no shading component and must have substantial variation in the pigment density distribution, simultaneously. We therefore propose an improved method, which uses two input skin images instead of one. In this improved method, one input image has no shading component and the other has substantial variation in pigment density distribution. To verify the effect of our method, we took images of four subjects and separated them into pigment components. We then compared the independence evaluation value of the separated signals extracted using our method and that of the conventional method. The results show that we obtain separated signals that have a better independence evaluation value by our method than by the conventional method.

Background: Demographic data of patients with sensorineural hearing loss (SNHL) in super-aged societies are still limited.Aims/objectives: To report audiometric statistics of SNHL and hearing aid (...

Aim: This study aimed to evaluate the effect of diet on serum lipids and to assess the effectiveness of long-term dietary therapy for hypertriglyceridemia. Methods: Seventy-nine patients (34 males and 45 females) with hypertriglyceridemia were enrolled and underwent dietary counseling for 12 months based on the following three recommendations: (1) reduce carbohydrate intake, (2) increase n-3 polyunsaturated fatty acid (PUFA) intake, and (3) limit alcohol drinking. We examined the effect of dietary therapy for 6 months on serum triglyceride (TG) levels and also compared the effectiveness of dietary and combined drug therapies on preventing arteriosclerotic disease from 7 to 12 months. Results: We observed that serum TG levels of the patients receiving dietary counseling were decreased compared with baseline at 6 months. Body weight and serum TG levels were decreased, and serum high-density lipoprotein levels were increased in the dietary therapy alone group, whereas BW, body mass index, and abdominal circumference were decreased in the combined drug treatment group compared with baselines at 6 and 12 months. Furthermore, the dietary therapy alone group demonstrated reductions in intake of total energy, carbohydrate, and saturated fatty acids, as well as n-6/n-3 PUFA ratio compared with baselines, but only n-6/n-3 PUFA ratio was decreased in the combined drug treatment group. Conclusion: This study demonstrated a decrease in serum TG level after 12 months of dietary therapy similar to drug therapy, which suggests that it is an effective treatment for hypertriglyceridemia, and heightened awareness should be made to encourage its use. The clinical trial registration number: UMIN000028860.

Currently, antimicrobial-resistant staphylococci, particularly methicillin-resistant Staphylococcus pseudintermedius (MRSP), are frequently isolated from canine superficial pyoderma in Japan. However, little is known regarding the nasal prevalence of MRSP in pet dogs. Here, we determined the prevalence of antimicrobial-resistant staphylococci in nares and affected sites of pet dogs with superficial pyoderma. Of the 125 nares and 108 affected sites of pet dogs with superficial pyoderma, 107 (13 species) and 110 (eight species) staphylococci strains, respectively, were isolated. The isolation rate of S. pseudintermedius from pyoderma sites (82/110 strains, 74.5%) was significantly higher than that from nares (57/107 strains, 53.3%) (P

Lung cancer is the most common cause of death in all kinds of cancers in Japan, and the number of it increased year and year in these 50 years. Since the 5-year survival rate of advanced lung cancer is only 6.4%, it is one of the poorest prognosis cancers. Almost 70% of patients with advanced lung cancer is suggested to be in precachexia/cachexia stage at their diagnosis. Cancer cachexia is one of the major reasons of refractory to chemotherapy and cancer death, however there is no effective treatment developed. Because cancer cachexia is multifactorial syndrome, multimodal treatment is needed. Anamorelin, a novel selective ghrelin receptor agonist, is under development for treating cancer cachexia. It has promising results in improving lean body mass in patients with advanced non-small cell lung cancer(NSCLC)and gastrointestinal cancer who suffer from cancer cachexia. The trial for early induction of multimodal intervention, Nutrition and Exercise Treatment for Advanced Cancer(NEXTAC)program, showed excellent feasibility and safety in elderly patients with advanced NSCLC and pancreatic cancer. These trials can develop a novel method for the treatment of cancer cachexia.

Cancer immunotherapy, including atezolizumab monotherapy, is a promising alternative strategy for patients with advanced non-small-cell lung cancer (NSCLC). Several inflammatory indices have been reported as potential biomarkers regarding the effectiveness of various treatments. This study aimed to analyze the efficacy of atezolizumab monotherapy using baseline inflammatory markers in NSCLC patients. We retrospectively enrolled 81 NSCLC patients who received atezolizumab monotherapy at six different medical institutions in Japan. The Cox proportional hazards model was used to assess the impact of the clinical variables, including inflammatory indexes, on clinical outcomes. Median progression-free survival (PFS) and overall survival (OS) were 60 days and 252 days, respectively. The objective response rate was 7.4%, and the disease control rate was 54.3%. Patients with high neutrophil to lymphocyte ratio (NLR), low lymphocyte to monocyte ratio (LMR), and/or high platelet to lymphocyte ratio (PLR), at baseline, demonstrated substantially shorter PFS and OS compared to those with a low NLR, high LMR, and/or low PLR. The multivariate analysis demonstrated that a high baseline NLR was substantially associated with short PFS and short OS. Our retrospective observations suggest that inflammatory indices may be a potential negative prognostic factor of atezolizumab monotherapy outcomes in NSCLC patients.

Combined immunotherapy and chemotherapy is a promising standard treatment in patients with advanced non-small cell lung cancer (NSCLC). This study aimed to evaluate the relationship between the combined therapy and pretreatment serum antinuclear antibody (ANA) levels as a prognostic indicator in patients with NSCLC. We retrospectively analyzed patients with advanced NSCLC who were treated with combinatorial immunotherapy and chemotherapy between January and December 2019 at six institutions in Japan. Relationship between ANA status and patients’ characteristics were reviewed. A total of 77 patients with advanced NSCLC were enrolled in the study. Patients were divided into ANA-positive (ANA ≥ 1:160) and ANA-negative (ANA

AIM The aims of this study were to: (a) describe the physical activity (PA) and quality of life (QOL) in living donor liver transplant (LDLT) recipients pre-operatively and at 3 months and 6 months post-operatively; (b) compare PA and QOL at 6 months post-operatively with a healthy control group; and (c) explore pre-operative factors that predict PA changes. METHODS Patients over 20 years of age who were undergoing LDLT were recruited. PA was measured based on the number of steps/day and time spent performing moderate-to-vigorous PA (MVPA) during 1 week using an accelerometer. QOL was assessed based on a physical (PCS) and mental (MCS) component summary of the eight-item Short-Form Health Survey. The LDLT and healthy control groups were matched for age (±3 years) and gender. Pre-operative factors predicting a change in PA were calculated using a generalized linear mixed model. RESULTS Twenty-four patients completed the study. By 6 months post-LDLT, the MCS and PCS were comparable to those in the control group. The number of steps (3,887 steps/day) and MVPA (29.3 min/week) showed significant improvement by 6 months post-operatively, but remained much lower compared with those in the control group. The multivariate analysis showed that younger age (p

The contribution of physical activity (PA) to the prevention of metabolic abnormalities following liver transplantation (LT) has not been well documented. We aimed to assess PA in post-LT patients and to quantify its relationships with the development of postoperative metabolic abnormalities and health-related quality of life (HRQOL). We recruited 111 patients who had undergone LT ≥ 6 months previously. PA was measured by accelerometry, and HRQOL was evaluated using SF-8. PA was quantified as the number of steps per day, and the time spent performing moderate-to-vigorous PA and light PA per week. The prevalence of hypertension, diabetes, and dyslipidemia increased more than twofold following LT. The proportion of the participants with a sedentary lifestyle (

Mycobacterium shigaense has recently been recognized as an emerging human pathogen, and is well known as a skin pathogen in immunocompromised individuals. In this report we describe the first case of chronic pulmonary infectious disease caused by M. shigaense in an immunocompetent individual. Keywords: Chest computed tomography (CT) images, emerging infectious diseases, immunocompetent, Mycobacterium shigaense, Mycobacterium simiae complex, Pulmonary disease, skin disease

Background Although the beta-2 receptor agonist (B2RA) is occasionally prescribed in the prenatal period for women with preterm labor, few studies have referred to the long-term effects of intrauterine exposure to B2RA on fetus. We examined the association between intrauterine exposure to B2RA and asthma in the offspring. Methods We obtained data from a hospital-based birth cohort study conducted in Tokyo, Japan. The outcomes of interest were three indicators, consisting of current wheeze, current asthma and ever asthma at 5 years of age, based on the International Study of Asthma and Allergies in Childhood questionnaire. Logistic regression analysis was used to evaluate the association between intrauterine B2RA exposure and outcomes. To evaluate dose-dependent risk, we categorized children into three groups according to both the cumulative dose and duration (days) and conducted trend analysis. Results Of 1158 children, 94 (8.1%) were exposed to B2RA in utero, and 191 (16.5%), 111 (9.6%) and 168 (14.5%) children experienced current wheeze, current asthma and ever asthma, respectively. After adjusting for confounders, we found an increased risk of current asthma caused by B2RA exposure with an adjusted odds ratio of 2.04 (95% confidence interval: 1.02-4.05). Trend analysis showed that B2RA exposure in utero was associated with a dose-dependent increased risk of current asthma in terms of both cumulative dose and duration (p values for trend were 0.015 and 0.017, respectively). These results were similar to those for other outcome measures. Conclusion Exposure to B2RA in utero could be a risk for childhood asthma. This article is protected by copyright. All rights reserved.

To clarify how the pure-tone threshold (PTT) on the PTA predicts speech perception (SP) in elderly Japanese persons.Data on PTT and SP were cross-sectionally analyzed in Japanese persons (656 ears in 353 patients, aged ≥65 years). Correlations of SP and average PTT in all tested frequencies were evaluated by Pearson's correlation coefficient and simple linear regression. After adjusting for sex, laterality of ears, and age, the relationship of average and frequency-specific PTT with impaired SP ≤50% was estimated by logistic regression models.SP correlated well (r = -0.699) with the average PTT of all tested frequencies. On the other hand, the correlation between patient age and SP was weak, especially among ≤85-year-old persons (r = -0.092). Linear regression showed that the average PTT corresponding to SP of 50% was 76.4 dB nHL. Odds ratios for impaired SP were highest for PTT at 2000 Hz. Odds ratios were higher for middle (500, 1000, 2000 Hz) and high frequencies (4000, 8000 Hz) than low frequencies (125, 250 Hz).The PTT on the pure-tone audiogram (PTA) is a good predictor of SP by speech audiometry among older persons, which could provide clinically important information for hearing aid fitting and cochlear implantation.

Fusion images of diffusion-weighted whole-body imaging with background body signal suppression and T2-weighted image (DWIBS/T2) demonstrate a strong signal for malignancies, with a high contrast against the surrounding tissues, and enable anatomical analysis. In the present study, DWIBS/T2 was compared with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for diagnosing cancer in the abdomen. Patient records, including imaging results of examination conducted between November 2012 and May 2014, were analyzed retrospectively. In total, 10 men (age, 73.6±9.6 years) and 8 women (age, 68.9±7.1 years) were enrolled into the current study. Of the enrolled patients, 2 were diagnosed with hepatocellular carcinoma, 1 with cholangiocellular carcinoma, 1 with liver metastasis, 2 with pancreatic ductal adenocarcinoma, 1 with renal cell carcinoma and 1 with malignant lymphoma. Benign lesions were also analyzed, including adenomyomatosis of the gallbladder (5 patients), intraductal papillary mucinous neoplasm (4 patients) and right adrenal adenoma (1 case). All the patients with cancer showed positive results on DWIBS/T2 images. However, only 7 out of 8 patients were positive with PET/CT. One patient with right renal cellular carcinoma was positive with DWIBS/T2, but negative with PET/CT. All the patients with benign lesions were negative with DWIBS/T2 and PET/CT. In conclusion, DWIBS/T2 was more sensitive in diagnosing cancer of organs in the abdominal cavity compared with PET/CT. Furthermore, negative results with DWIBS/T2 and PET/CT were useful for the diagnosis of benign lesions, such as adenomyomatosis of the gallbladder and intraductal papillary mucinous neoplasm.