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Aim: Given the adverse effects of anticholinergic drugs and the necessity for medication evaluation tools in the aging population, a comprehensive scale to assess the total anticholinergic burden in Japan was developed. We examined the longitudinal association between the anticholinergic burden, quantified using the Japanese Anticholinergic Drug Risk Scale, and the development of frailty and sarcopenia in older adults., Methods: In this longitudinal population-based cohort study, 2044 older residents without long-term care needs were randomly selected from a community in Kashiwa, Japan. Baseline data were collected in 2012, with follow-ups in 2013, 2014, 2016, 2018, and 2021. Medications were identified through interviews and assessed with the Screening Tool for Older Persons' Appropriate Prescriptions for the Japanese. The anticholinergic burden was quantified using the Japanese Anticholinergic Risk Scale. We evaluated new-onset frailty and sarcopenia using the Cardiovascular Health Study Index and Asian Working Group for Sarcopenia 2019 criteria, respectively., Results: Of the 1549 participants without sarcopenia or frailty at baseline (age 72.5 ± 5.5 years; 49.1% women; median follow-up 6.0 years), 274 and 230 developed new-onset frailty and sarcopenia, respectively, during follow-up. After adjusting for potential confounders, an anticholinergic burden score ≥3 was strongly associated with new-onset frailty and sarcopenia (adjusted hazard ratio [95% confidence interval]: 2.45 [1.52-3.94] and 2.01 [1.20-3.35], respectively)., Conclusions: Anticholinergic burden is a predictor of frailty and sarcopenia in community-dwelling older adults. Effective evaluation and management of anticholinergic burden using the Japanese Anticholinergic Drug Risk Scale are crucial for promoting healthy aging and mitigating adverse health outcomes. Geriatr Gerontol Int 2025; ••: ••-••., (© 2025 The Author(s). Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Astragaloside IV (As-IV), a key component of traditional Japanese Hozai tonics, has a steroid skeleton like estrogen. It inhibits vascular calcification via estrogen receptor α, offering cardiovascular benefits. However, its estrogen-like properties promote breast cancer cell proliferation. Targeted research is needed to optimize cardiovascular preventive effects without adverse effects., (© 2024 The Author(s). Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Background: Engagement in non-exercise physical activities (NEPA) has a significant correlation with health. This study aimed to compare the impact of moderate-to-vigorous-intensity NEPA and exercise habit (EH) on frailty among community-dwelling older adults., Methods: This study utilized data from the Kashiwa cohort study in Japan, with baseline assessments in 2014 with a 7-year follow ups (4.0 [2.0-7.0]). A total of 1,288 participants were included. Frailty was assessed using the Cardiovascular Health Study Index, NEPA through the Global Physical Activity Questionnaire, and EH via self-reported exercise engagement at each follow-up examination. Generalized estimating equations (GEE) and Cox regression analyses were used to estimate associations between NEPA, EH, and frailty., Results: Compared to participants with no NEPA nor EH, those with NEPA only, with EH only, and with both showed significantly lower adjusted odds ratio (95 %CI) of frailty: 0.29 (0.16-0.52), 0.21 (0.11-0.41) and 0.21 (0.12-0.36). NEPA and EH at baseline were predictor variables for new-onset frailty during the 7-year follow-up period, with adjusted hazard ratios (95 % CI) of 0.55 (0.33-0.92) for NEPA only, 0.51 (0.29-0.90) for EH only, and 0.42 (0.25-0.70) for both. No significant differences were observed between the associations of NEPA and EH with frailty., Conclusions: NEPA is associated with lower frailty risk in older adults, with a similar but non-additive effect to that of EH. These findings highlight the importance of NEPA for frailty prevention, particularly for those not engaged in formal exercise programs., Competing Interests: Declaration of competing interest There are no financial conflicts or other conflicts of interest to declare., (Copyright © 2025. Published by Elsevier B.V.)

Purpose: Ikigai, a psychological concept in Japanese culture representing a life worth living, contributes to health outcomes. This study examined the association between Ikigai and the incidence of frailty and sought to investigate the underlying biological mechanism by exploring inflammatory cytokines., Materials and Methods: In the 2016 Kashiwa Cohort Study, 832 community-dwelling older adults without frailty were enrolled. Participants reported their Ikigai status at baseline. Frailty was defined as meeting three of Fried's five phenotypic criteria. Plasma concentrations of inflammatory cytokines, including interleukins (ILs) and tumor necrosis factor α, were measured at baseline using immunoassays. Cox regression was used to analyze the association between Ikigai and new-onset frailty stratified by sex after adjusting for relevant confounders., Results: Overall, 7.1 % of 832 participants (75.8 ± 4.7 years, women 47.0 %) developed new-onset frailty during the 5-year follow-up. Older adults with Ikigai (n = 749) had better vitality and mental health and fewer depressive symptoms than those without Ikigai. In women, Ikigai was associated with a lower risk of developing frailty (a fully-adjusted hazard ratio=0.24, 95 % confidence interval: 0.08-0.73, P = 0.012). Notably, a significantly lower prevalence of exhaustion was observed in women with Ikigai (P < 0.001). A higher concentration of IL-6 was observed in women with Ikigai at baseline than in those without Ikigai who developed frailty (P = 0.036)., Conclusions: This study demonstrated that Ikigai could prevent frailty in women, which might be attributed to mitigate exhaustion. Furthermore, the biological actions of Ikigai are associated with high IL-6 levels. Our findings suggest that sex-specific frailty prevention should be considered with Ikigai., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bo-Kyung SON reports financial support was provided by the Ministry of Education, Culture, Sports, Science and Technology of Japan. Bo-Kyung SON reports financial support was provided by The Japan Geriatrics Society. Bo-Kyung SON reports financial support was provided by Japan Science and Technology Agency. If there are other authors, they 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 © 2025. Published by Elsevier B.V.)

As fluoroscopy-guided interventional procedures gain popularity, the associated health threats from radiation exposure to interventionalists during these procedures are increasing. Therefore, an understanding of the potential risks of radiation and careful consideration on minimizing exposure to radiation during the procedures are of paramount importance. The Korean Pancreatobiliary Association has developed a clinical practice guideline to minimize radiation exposure during fluoroscopy-guided interventional procedures. This guideline provides recommendations to deal with the risk of radiation exposure to interventionalists who perform fluoroscopy-guided procedures, and emphasizes the importance of proper and practical approaches to avoid unnecessary radiation exposure.

Purpose: A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer., Methods: Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed., Results: Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B ( CDKN1B ) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B -targeted approaches and these drugs., Conclusion: The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer., Competing Interests: The authors declare that they have no competing interests., (© 2024 Korean Breast Cancer Society.)

Aim: Vascular aging is an important risk factor for cardiovascular diseases, including abdominal aortic aneurysm (AAA) and pathological aortic dilatation, playing a critical role in the morbidity and mortality of older adults. Vascular calcification, a phenotype of vascular aging, is frequently associated with AAA. However, this association remains unclear owing to the lack of animal models. This study investigated the effects of a high-phosphate diet (HPD), a prominent trigger of vascular calcification in AAA., Methods: Eight-week-old male mice were fed either a normal diet (ND; Ca 1.18%/P 1.07% = 1.10) or an HPD (Ca 1.23%/P 1.65% = 0.75) for 4 weeks. Subsequently, AAA was induced using CaCl 2 application and angiotensin II (AngII) infusion for 4 weeks., Results: The HPD resulted in more pronounced AAA formation than did the ND. Importantly, vascular calcification was observed only in the aorta of the HPD mice. Enhanced Runt-related transcription factor 2 expression and apoptosis (downregulation of growth arrest-specific gene 6/pAkt survival pathway), two major mechanisms of vascular calcification, were also observed. Furthermore, increased IL-6 and F4/80 expression was observed in the aorta of HPD mice. In RAW264.7 cells, inorganic phosphate enhanced IL-6 and IL-1β expression under AngII priming. Ferric citrate, a phosphate binder, significantly inhibited HPD-induced AAA formation., Conclusions: These findings suggest that HPD induces vascular calcification and AAA formation, possibly through inflammation. This murine model suggests that vascular calcification induced by phosphate burden may be a therapeutic target for vascular diseases, including AAA. Geriatr Gerontol Int 2024; 24: 973-981., (© 2024 The Author(s). Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Background and Objectives : This study aimed to elucidate the cytologic characteristics and diagnostic usefulness of endoscopic ultrasonography-fine needle aspiration cytology (EUS-FNAC) by comparing it with liquid-based preparation (LBP) and conventional smear (CS) in pancreas. Methods : The diagnostic categories (I through VII) were classified according to the World Health Organization Reporting System for Pancreaticobiliary Cytopathology. Ten cytologic features, including nuclear and additional features, were evaluated in 53 cases subjected to EUS-FNAC. Nuclear features comprised irregular nuclear contours, nuclear enlargement, hypochromatic nuclei with parachromatin clearing, and nucleoli. Additional cellular features included isolated atypical cells, mucinous cytoplasm, drunken honeycomb architecture, mitosis, necrotic background, and cellularity. A decision tree analysis was conducted to assess diagnostic efficacy. Results : The diagnostic concordance rate between LBP and CS was 49.1% (26 out of 53 cases). No significant differences in nuclear features were observed between categories III (atypical), VI (suspicious for malignancy), and VII (malignant). The decision tree analysis of LBP indicated that cases with moderate or high cellularity and mitosis could be considered diagnostic for those exhibiting nuclear atypia. Furthermore, in CS, mitosis, isolated atypical cells, and necrotic background exerted a more significant impact on the diagnosis of EUS-FNAC. Conclusions : Significant parameters for interpreting EUS-FNAC may differ between LBP and CS. While nuclear atypia did not influence the diagnosis of categories III, VI, and VII, other cytopathologic features, such as cellularity, mitosis, and necrotic background, may present challenges in diagnosing EUS-FNAC.

Aim: Although the maintenance and improvement of quality of life (QoL) through holistic care are important in geriatric medical care, care priorities might differ depending on three essential aspects of QoL: the quality of daily living, satisfaction and happiness from birth to death, and human vitality, which are "Seikatsu," "Jinsei," "Seimei" in Japanese, respectively. We aimed to clarify these priorities in terms of medical care and examined how the definitions of QoL affected these priorities' rankings., Methods: This cross-sectional study involved community-dwelling older adults aged ≥65 years living in Kashiwa City, Chiba Prefecture, Japan. The number of participants was 1550 (mean age, 76.1 ± 5.8 years; 699 women [45.1%]). A self-administered questionnaire distributed in advance was used to rank 12 items sought in medical care. Participants were randomly assigned to one of three groups and sent the corresponding questionnaire, which differed only in the definition of QoL., Results: The top priorities for medical care were "effective treatment of illness," "improvement of physical function," and "maintaining a high level of activity." When QoL was defined as "the quality of daily living, satisfaction and happiness from birth to death, and human vitality," participants were significantly more likely to rank QoL improvement as one of the top three items (adjusted odds ratio, 1.46; 95% confidence interval, 1.03-2.05)., Conclusions: As a medical care priority, older adults desire improvement of multidimensional elements of life, including human vitality. Health care providers should consider this when making medical care decisions. Geriatr Gerontol Int 2024; 24: 493-498., (© 2024 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Introduction: The CLDN18 gene, encoding claudin 18.1 and claudin 18.2, is a key component of tight junction strands in epithelial cells that form a paracellular barrier that is critical in Stomach Adenocarcinoma (STAD)., Methods: Our study included 1,095 patients with proven STAD, 415 from The Cancer Genome Atlas (TCGA) cohort and 680 from the Gene Expression Omnibus database. We applied various analyses, including gene set enrichment analysis, pathway analysis, and in vitro drug screening to evaluate survival, immune cells, and genes and gene sets associated with cancer progression, based on CLDN18 expression levels. Gradient boosting machine learning (70% for training, 15% for validation, and 15% for testing) was used to evaluate the impact of CLDN18 on survival and develop a survival prediction model., Results: High CLDN18 expression correlated with worse survival in lymphocyte-poor STAD, accompanied by decreased helper T cells, altered metabolic genes, low necrosis-related gene expression, and increased tumor proliferation. CLDN18 expression showed associations with gene sets associated with various stomach, breast, ovarian, and esophageal cancers, while pathway analysis linked CLDN18 to immunity. Incorporating CLDN18 expression improved survival prediction in a machine learning model. Notably, nutlin-3a and niraparib effectively inhibited high CLDN18-expressing gastric cancer cells in drug screening., Conclusion: Our study provides a comprehensive understanding of the biological role of CLDN18-based bioinformatics and machine learning analysis in STAD, shedding light on its prognostic significance and potential therapeutic implications. To fully elucidate the molecular intricacies of CLDN18, further investigation is warranted, particularly through in vitro and in vivo studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Recently, novel Kirsten rat sarcoma viral oncogene homolog (KRAS) inhibitors have been clinically developed to treat KRAS G12C-mutated non-small cell lung cancer (NSCLC) patients. However, achieving complete tumor remission is challenging. Therefore, the optimal combined therapeutic intervention with KRAS G12C inhibitors has a potentially crucial role in the clinical outcomes of patients. We investigated the underlying molecular mechanisms of adaptive resistance to KRAS G12C inhibitors in KRAS G12C-mutated NSCLC cells to devise a strategy preventing drug-tolerant cell emergence. We demonstrate that AXL signaling led to the adaptive resistance to KRAS G12C inhibitors in KRAS G12C-mutated NSCLC, activation of which is induced by GAS6 production via YAP. AXL inhibition reduced the viability of AXL-overexpressing KRAS G12C-mutated lung cancer cells by enhancing KRAS G12C inhibition-induced apoptosis. In xenograft models of AXL-overexpressing KRAS G12C-mutated lung cancer treated with KRAS G12C inhibitors, initial combination therapy with AXL inhibitor markedly delayed tumor regrowth compared with KRAS G12C inhibitor alone or with the combination after acquired resistance to KRAS G12C inhibitor. These results indicated pivotal roles for the YAP-GAS6-AXL axis and its inhibition in the intrinsic resistance to KRAS G12C inhibitor., Competing Interests: Declaration of competing interest T. Yamada received commercial research grants from Pfizer, Ono Pharmaceutical, Janssen Pharmaceutical K.K., AstraZeneca, and Takeda Pharmaceutical Company Limited and has received speaking honoraria from Eli Lilly. H. Kawachi received personal fees from Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., AstraZeneca KK, Taiho Pharmaceutical Co. Ltd., Eli Lilly Japan KK, and MSD KK, outside the purview of the submitted work. N. Furuya received personal fees from AstraZeneca, Chugai, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, MSD, Pfizer, Taiho, and Novartis. S. Watanabe received grants and personal fees from Boehringer Ingelheim and Nippon Kayaku. Personal fees from Lilly, Pfizer, Novartis Pharma, AstraZeneca, Chugai Pharma, Bristol-Myers, Ono Pharmaceutical, Daiichi Sankyo, and Taiho Pharmaceutical. S. Yano received research grants from Chugai Pharmaceutical and Boehringer-Ingelheim and has received speaking honoraria from Amgen, Chugai Pharmaceutical, Boehringer-Ingelheim, Novartis, and Pfizer. T. Sakai received research grants from Otsuka Pharmaceutical, Taiho Pharmaceutical and Oncolys BioPharma, and a patent fee from JT Pharmaceutical. K. Takayama reports receiving research grants from Chugai-Roche Co., and Ono Pharmaceutical Co., and personal fees from AstraZeneca Co., Chugai-Roche Co., MSD-Merck Co., Eli Lilly Co., Boehringer-Ingelheim Co., and Daiichi-Sankyo Co.No potential conflicts of interest were disclosed by the other authors., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: This study aimed to determine the longitudinal associations of the coexistence of frailty and depressive symptoms with mortality among older adults., Methods: The study participants were community-dwelling older adults aged ≥65 years who participated in the baseline survey of the Kashiwa Cohort Study in Japan in 2012. We used Fried's frailty phenotype criteria to classify participants as non-frail (score = 0), pre-frail (1 or 2), or frail (≥3). Depressive symptoms were assessed using the GDS-15 (≥6 points). Cox proportional hazards models were used to evaluate the association of co-occurring frailty and depressive symptoms with all-cause mortality, after adjusting for sociodemographic and clinical characteristics., Results: The study included 1920 participants, including 810 non-frail, 921 pre-frail, and 189 frail older adults, of which 9.0 %, 15.7 %, and 36.0 %, respectively, had depressive symptoms. Ninety-one (4.7 %) participants died during the average follow-up period of 4.8 years. Compared with non-frail participants without depressive symptoms, frail participants had greater adjusted hazard ratios for mortality: 2.47 (95 % CI, 1.16 to 5.25) for frail participants without depressive symptoms and 4.34 (95 % CI, 1.95 to 9.65) for frail participants with depressive symptoms. However, no statistically significant associations were observed in non-frail or pre-frail participants irrespective of depressive symptoms., Conclusion: Frail older adults with depressive symptoms have a substantially greater risk of mortality. Screening for depressive symptoms and frailty in older adults should be incorporated into health checkups and clinical practice to identify high-risk populations., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Aim: Chronic inflammation is a pathophysiological cause of age-related diseases, including frailty. Although diet is a determinant of inflammation, few prospective studies have investigated its role in frailty onset. This study used the dietary inflammatory index to investigate whether a proinflammatory diet affects the incidence of frailty in a 7-year follow-up of older Japanese adults., Methods: We enrolled community-dwelling older adults without frailty from the 2014 Kashiwa cohort study. Energy-adjusted dietary inflammatory index (E-DII) scores were calculated using a brief self-administered diet history questionnaire. Serum high-sensitivity C-reactive protein (hsCRP) levels were measured by immunoassays. Frailty was defined as meeting three of Fried's five phenotypic criteria. Cox regression was used to analyze associations between E-DII scores and new-onset frailty after adjusting for relevant confounders., Results: Overall, 95 (11.7%) of 811 participants (73.7 ± 4.8 years, women 47.3%) developed new-onset frailty during the 7-year follow-up. The baseline E-DII scores significantly correlated with log-hsCRP levels, even after adjustment (β = 0.075, P = 0.035). The highest tertile of E-DII scores (proinflammatory diet) showed a 2.03 times (95% confidence interval, 1.22-3.36) higher risk of new-onset frailty than that associated with the lowest tertile (P = 0.006). When E-DII was calculated on the basis of anti-inflammatory food parameters only, the highest tertile showed a 2.32 times (95% confidence interval, 1.36-3.95) higher risk than that associated with the lowest tertile (P = 0.002)., Conclusions: E-DII scores significantly correlated with serum hsCRP levels. High E-DII scores caused by low intake of anti-inflammatory foods are associated with frailty incidence. For community-dwelling older adults, dietary interventions that lower E-DII scores (e.g., encouraging dietary fiber intake) may help prevent frailty. Geriatr Gerontol Int 2024; 24: 189-195., (© 2023 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Aim: This study aims to elucidate what volunteering activities mean for older adults in Japan by analyzing their emotions and evaluations from hedonic (e.g., happiness), eudaimonic (e.g., self-growth), and social (e.g., social coherence) well-being., Methods: The qualitative research was conducted to describe the subjective experience of older adults' volunteering activities (frailty checkups) in the community-setting. Eight older adults were interviewed about their experiences during these activities. The interview data were analyzed from two assumption frameworks: first, three aspects of well-being, and second, timeframes of well-being, during the activity, medium-term, and long-term. Previous studies have not focused on the polysemy or the timeframe of well-being., Results: Our results showed that hedonic, eudaimonic, and social well-being are not independent, but overlap. Furthermore, even if older adults experience certain emotions at a point of time, they may change in the long term. This implies that it is important to analyze older adults' feelings and experiences from not only one aspect but from different perspectives and measure their feelings not just at a particular moment but in the long term. This is the first empirical study to examine qualitatively the holistic experiences of well-being among older adults who volunteer., Conclusions: We conclude that this study is unique in that it attempted to associate empirically the experiences of older adults during volunteering with their general psychological status of well-being. These findings could help make volunteering activities more meaningful for older adults and create or promote an active community. Geriatr Gerontol Int 2024; 24: 273-278., (© 2024 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Purpose: Frailty was indicated to be closely related to older adults' lifestyles, especially in nutrition-related factors (such as balanced diet and oral functions), physical factors, and social factors in our previous study. Here, we developed an "Eleven-Check" (EC) questionnaire containing the aforementioned three factors. This study tested whether the EC questionnaire can estimate frailty in community-dwelling older adults., Materials and Methods: The study sample comprised 1,523 independent older adults. The primary outcome of frailty was assessed using the Cardiovascular Health Study index. The secondary outcome of sarcopenia was assessed by the criteria of the Asian Working Group for Sarcopenia 2019. The EC questionnaire comprised 11 dichotomous factors related to nutrition-related (diet and oral functions), physical, and social factors., Results: Frailty prevalence was 8.5 % (76.1 ± 5.8y, 45.1 % women). The accuracy of the EC questionnaire for frailty was optimal when the total scores of 4/5 were used as the threshold. Compared to the low-risk group (<5), the high-risk group (≥5) had a significant association between frailty with an adjusted odds ratio (aOR) of 4.68 (95 %CI, 3.10-7.05). Moreover, the high-risk group also had a significant association with sarcopenia, with an aOR of 1.82 (1.27-2.61)., Conclusions: For community-dwelling older adults, the EC questionnaire was able to simply screen frailty and sarcopenia status. Further, it might raise older adults' self-awareness from a multifaceted perspective in their daily life to prevent steady decline and frailty sustainably in a community setting., Competing Interests: Declaration of Competing Interest There are no financial conflicts or other conflicts of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

Background: Tumor spread through air spaces (STAS) is a recently discovered risk factor for lung adenocarcinoma (LUAD). The aim of this study was to investigate specific genetic alterations and anticancer immune responses related to STAS. By using a machine learning algorithm and drug screening in lung cancer cell lines, we analyzed the effect of Janus kinase 2 (JAK2) on the survival of patients with LUAD and possible drug candidates., Methods: This study included 566 patients with LUAD corresponding to clinicopathological and genetic data. For analyses of LUAD, we applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analysis, in vitro drug screening, and gradient boosting machine (GBM) analysis., Results: The patients with STAS had a shorter survival time than those without STAS ( P < 0.001). We detected gene set-related downregulation of JAK2 associated with STAS using GSEA. Low JAK2 expression was related to poor prognosis and a low CD8+ T-cell fraction. In GBM, JAK2 showed improved survival prediction performance when it was added to other parameters (T stage, N stage, lymphovascular invasion, pleural invasion, tumor size). In drug screening, mirin, CCT007093, dihydroretenone, and ABT737 suppressed the growth of lung cancer cell lines with low JAK2 expression., Conclusion: In LUAD, low JAK2 expression linked to the presence of STAS might serve as an unfavorable prognostic factor. A relationship between JAK2 and CD8+ T cells suggests that STAS is indirectly related to the anticancer immune response. These results may contribute to the design of future experimental research and drug development programs for LUAD with STAS., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Aim: As associations between oral function and general health have been reported in community-dwelling older adults, easily implementable preventive measures are urgently required. We focused on the health benefits of gum chewing, as no studies have been carried out on the impact of gum-chewing routines on the health of older adults. This cross-sectional study aimed to determine whether the gum-chewing routine is associated with oral, physical and cognitive functions in community-dwelling older adults., Methods: This study included 1617 community-dwelling older participants in a health survey carried out in 2021. The gum-chewing routine and weekly chewing time were assessed using a self-administered questionnaire. The outcome measures, including actual measurements of oral function, physical function, cognitive function, dietary intake and lifestyle, were evaluated using self-administered questionnaires or health surveys., Results: We analyzed 1474 (mean age 76.1 ± 5.8 years, 45% women) participants for whom all data were not missing, and 14% of them had a gum-chewing routine for more than 30 min weekly. Oral functions were significantly higher in older adults with a gum-chewing routine, and there were substantially fewer participants with oral frailty (adjusted odds ratio 0.581, 95% confidence interval 0.340-0.993). Additionally, cognitive and physical functions, including grip strength, were significantly higher in the gum-chewing routine group., Conclusions: Community-dwelling older adults with a gum-chewing routine have higher oral, physical and cognitive functions. These findings indicate that a gum-chewing routine might contribute to maintaining oral function and preventing frailty. Geriatr Gerontol Int 2024; 24: 68-74., (© 2023 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Competing Interests: The authors declare no conflict of interest.

This study aimed to elucidate the clinicopathological significance of chemerin immunohistochemical expression in colorectal cancer (CRC) based on histologic components. Immunohistochemistry was performed to detect chemerin in 266 human CRC tissues. Correlation between chemerin expression, clinicopathological characteristics, and survival in CRC. A meta-analysis was performed to claify the prognostic role of chemerin tissue expression in malignant tumors. Chemerin was expressed in 125 of 266 CRC tissues (47.0 %) and was significantly correlated with distant metastasis (P = 0.012). However, no significant correlation was observed between chemerin expression and other clinicopathological parameters. Subgroup analyses based on histological components showed that chemerin expression was significantly higher in CRCs with the mucinous component than in those without the mucinous component (P 0.001). However, there was no significant correlation between chemerin expression and the micropapillary component. Patients with chemerin expression had worse overall and recurrence-free survival rates (P = 0.017 and P = 0.009, respectively). The prognostic significance of chemerin was found in CRCs without the mucinous component but not in those with the mucinous component. Chemerin expression was significantly correlated with poor survival in breast and ovarian cancers in the meta-analysis. Chemerin expression significantly correlated with distant metastasis and poor survival in CRCs. The predictive role of patient prognosis is useful for CRCs, especially those with no mucinous component., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest or financial disclosures., (Copyright © 2023. Published by Elsevier GmbH.)

The aim of this study was to evaluate the clinicopathological significance and associated signaling pathways of p21-activated kinase 1 (PAK1) in colorectal cancer (CRC). PAK1 immunohistochemical expression was investigated in 246 human CRC tissues to evaluate its clinicopathological significance and prognostic role. Correlations between PAK1 and the immunoscore, HIF-1α, and pFOXO1 were also evaluated. PAK1 was expressed in 169 of 246 CRC tissues (68.7%). PAK1 expression significantly correlated with the metastatic lymph node ratio (P = 0.023). However, PAK1 expression did not correlate with tumor size, tumor location, tumor differentiation, lymphovascular and perineural invasion, or distant metastasis. PAK1 expression was significantly higher in CRC with a low immunoscore than in CRC with a high immunoscore (P = 0.017). In addition, there were significant correlations between PAK1, HIF-1α, and pFOXO1 expression (P = 0.001 and P = 0.024, respectively). Patients with PAK1 expression had worse overall and recurrence-free survival than those without PAK1 expression (P 0.001 and P = 0.001, respectively). PAK1 expression was significantly correlated with worse prognosis in CRCs patients. In addition, PAK1 expression was significantly correlated with a low immunoscore and high expression of HIF-1α and pFOXO1 in CRCs., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest or financial disclosures., (Copyright © 2023. Published by Elsevier GmbH.)

This study aimed to evaluate the clinicopathological significance and prognostic role of fatty acid-binding protein 4 (FABP4) expression in colorectal cancer (CRC). Nuclear expression of FABP4 was investigated by immunohistochemistry for FABP4 on 246 human CRC tissues. The correlations between FABP4 expression, and clinicopathological characteristics and survival, was evaluated in patients with CRC. FABP4 was expressed in 91 of the 246 CRC tissues (37.0%). FABP4 expression was significantly correlated with older age, right-sided colon cancer, perineural invasion, higher pT stage, lymph node metastasis, and higher pTNM stage. However, there was no significant correlation between FABP4 expression and sex, tumor size, tumor differentiation, vascular or lymphatic invasion, or distant metastasis. Nuclear FABP4 expression was not significantly correlated with cytoplasmic FABP4 expression (P = 0.412). FABP4 expression was significantly correlated with nuclear pNF-κB expression (P = 0.001), and was significantly higher in CRC with a low immunoscore than in CRC with a high immunoscore (P < 0.001). There were significant correlations between FABP4 expression and worse overall and recurrence-free survival rates (P < 0.001 and P = 0.007, respectively). FABP4 expression was significantly correlated with aggressive tumor behaviors and pathological characteristics. In addition, patients with CRC with FABP4 expression had worse survival rates., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest or financial disclosures., (Copyright © 2023. Published by Elsevier GmbH.)

Objectives: The hypertriglyceridaemic waist (HTGW) phenotype, an indicator to assess metabolic syndrome, could be a useful predictive marker for the risk of acute pancreatitis. This study aimed to evaluate the association between the HTGW phenotype and the risk of acute pancreatitis with a nationwide population-based cohort., Design: A retrospective, nationwide cohort study., Setting: Registry of health check-up result from Korean National Health Insurance Service., Participants: A total of 3 912 551 adults who underwent health checkups under the National Health Insurance Service in 2009 were enrolled in this study., Interventions: Subjects with both increased waist circumference (WC) and elevated blood triglyceride concentrations were defined as the HTGW phenotype. The participants were divided into four groups, classified as NWNT (normal WC-normal triglycerides), EWNT (elevated WC-normal triglycerides), NWET (normal WC-elevated triglycerides) and HTGW. The WC triglyceride index (WTI) is a quantitative indicator of the HTGW phenotype which is calculated by multiplying WC (cm) by triglyceride levels (mmol/L)., Primary Outcome Measure: The subjects were followed until 31 December 2018. The adjusted HRs of acute pancreatitis in each group were estimated., Results: During the follow-up, there were a total of 8933 of acute pancreatitis occurrences. The incidence of acute pancreatitis in all subjects was 0.278 per 1000 person-year. The HTGW group had the highest incidence (0.444), followed by the NWET (0.381), and EWNT (0.316) groups. The HTGW group had a significant higher incidence of acute pancreatitis than the NWNT groups (HR 1.364 (95% CI 1.279 to 1.454)). The risk of acute pancreatitis steadily increased as the WTI increased (HR 1.847 (95% CI 1.657 to 2.058) in 10th decile)., Conclusions: The HTGW phenotype is confirmed to be an independent risk factor that increases the risk of acute pancreatitis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study aimed to compare the diagnostic accuracy of the Ki-67 labeling index (LI) between endoscopic ultrasonography-fine-needle aspiration cytology/biopsy (EUS-FNAC/FNB) and surgical specimens of pancreatic neuroendocrine neoplasms (PanNENs)., Methods: Conventional meta-analysis and diagnostic test accuracy (DTA) reviews were performed on 17 eligible studies. The DTA review involved calculating the sensitivity, specificity, diagnostic odds ratio (OR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve. In addition, subgroup analysis was conducted based on EUS-FNAC and FNB, tumor grade, and tumor size., Results: The overall concordance rate of WHO grade based on Ki-67 LI between the EUS-FNAC/FNB and the surgical specimen was 0.767 (95% confidence interval (CI), 0.713-0.814). Concordance rates of the EUS-FNAC and EUS-FNB subgroups were 0.741 (95% CI, 0.681-0.794) and 0.839 (95% CI, 0.738-0.906), respectively. In the DTA review for grade 3, the sensitivity and specificity were calculated to be 0.786 (95% CI, 0.590-0.917) and 0.998 (95% CI, 0.987-1.000), respectively. The diagnostic OR and AUC of the SROC curve were 150.220 (95% CI, 46.145-489.000) and 0.983, respectively. The sensitivity and specificity were observed to be highest in the grade 1 and 3 subgroups, respectively., Conclusions: Higher concordance of tumor grade based on Ki-67 LI was observed between EUS-FNAC/FNB and surgical specimens, indicating the potential usefulness of Ki-67 LI in predicting PanNEN tumor grade in EUS-FNAC/FNB.

Background: Clinical evidence demonstrating a longitudinal association between prescribed medications and sarcopenia onset is lacking. We investigated the association of polypharmacy (the use of five or more medications) and potentially inappropriate medications (PIMs) with sarcopenia risk in community-dwelling older adults., Methods: In this longitudinal population-based cohort study, 2,044 older residents with no long-term care needs were randomly selected from a community in Kashiwa, Japan. Baseline data collection was conducted in 2012, with follow-ups in 2013, 2014, 2016, 2018, and 2021. Prescribed medications and PIMs (drugs listed in the Screening Tool for Older Person's Appropriate Prescriptions for the Japanese or potentially muscle-wasting drugs) were identified through interviews. New-onset sarcopenia was identified according to the 2019 criteria of the Asian Working Group for Sarcopenia over a 9-year period and analyzed. We used Cox proportional hazards models to test the longitudinal association of prescribed medications with sarcopenia onset., Results: Of the 1,549 participants without sarcopenia at baseline (mean age, 72.5 ± 5.5 years; 49.1% women; median and interquartile range, 6.0 [4.0-9.0] years), 230 experienced new-onset sarcopenia during the follow-up. After adjusting for confounders, polypharmacy combined with PIM use was strongly associated with new-onset sarcopenia (adjusted hazard ratio, 2.35; 95% confidence interval, 1.58-3.51; P < 0.001). No significant associations were observed for either PIM use or polypharmacy alone., Conclusions: Polypharmacy combined with PIM use, but not polypharmacy alone, was associated with an increased risk of new-onset sarcopenia over the 9-year follow-up period among community-dwelling older adults. Limiting polypharmacy and imposing the prescription of appropriate medications may facilitate sarcopenia prevention., (© 2023. The Author(s).)

Frailty is an age-related condition characterized by a decline in physical capacity with an increased vulnerability to stressors. During the COVID-19 pandemic, there was considerable progression in frailty in older adults. Therefore, an online frailty check (FC) is required for continuous screening, especially acceptable to older adults. We aimed to co-design/co-develop an online FC application with FC supporters who were facilitators in a pre-existing onsite FC program in the community. It consisted of a self-assessment of sarcopenia and an 11-item questionnaire assessing dietary, physical, and social behaviors. Opinions obtained from FC supporters (median 74.0 years) were categorized and implemented. The usability was assessed using the system usability scale (SUS). For both FC supporters and participants (n = 43), the mean score was 70.2 ± 10.3 points, which implied a "marginally high" acceptability and a "good" adjective range. Multiple regression analysis showed that the SUS score was significantly correlated with onsite-online reliability, even after adjusting for age, sex, education level, and ICT proficiency (b = 0.400, 95% CI: 0.243-1.951, p = 0.013). We also validated the online FC score, which showed a significant association between onsite and online FC scores (R = 0.670, p = 0.001). In conclusion, the online FC application is an acceptable and reliable tool to check frailty for community-dwelling older adults.

Background/aims: This study aimed to investigate the patterns of preferred endoscopic procedure types and techniques for managing difficult common bile duct (CBD) stones in South Korea., Methods: The Committee of Policy and Quality Management of Korean Pancreatobiliary Association (KPBA) conducted a survey containing 19 questions. Both paper and online surveys were carried out; with the paper survey being conducted during the 2019 Annual Congress of KPBA and the online survey being conducted through Google Forms from April 2020 to February 2021., Results: The response rate was approximately 41.3% (86/208). Sixty-two (73.0%) worked at tertiary hospitals or academic medical centers, and 60 (69.7%) had more than 5 years of endoscopic retrograde cholangiopancreatography experience. The preferred size criteria for large CBD stones were 15 mm (40.6%), 20 mm (31.3%), and 30 mm (4.6%). For managing of large CBD stones, endoscopic papillary large balloon dilation after endoscopic sphincterotomy was the most preferred technique (74.4%). When performing procedures in those with bleeding diathesis, 64 (74.4%) respondents favored endoscopic papillary balloon dilation (EPBD) alone or EPBD with small endoscopic sphincterotomy. Fifty-five respondents (63.9%) preferred the doubleguidewire technique when faced with difficult bile duct cannulation in patients with periampullary diverticulum. In surgically altered anatomies, cap-fitted forward viewing endoscopy (76.7%) and percutaneous transhepatic cholangioscopy (48.8%) were the preferred techniques for Billroth-II anastomosis and total gastrectomy with Roux-en-Y anastomosis, respectively., Conclusions: Most respondents showed unifying trends for the management of difficult CBD stones. The current practice patterns could be used as basic data for clinical quality improvements in the management of difficult CBD stones.

Background/aims: Although endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) and fine needle biopsy (FNB) are widely used for tissue acquisition of pancreatic solid mass, the optimal strategy of this procedure has not been established yet. The aim of this nationwide study was to investigate the current practice patterns of EUS-FNA/FNB for pancreatic solid mass in Korea., Methods: The Policy-Quality Management of the Korean Pancreatobiliary Association (KPBA) developed a questionnaire containing 22 questions. An electronic survey consisting of the questionnaire was distributed by e-mail to members registered to the KPBA., Results: A total of 101 respondents completed the survey. Eighty respondents (79.2%) performed preoperative EUS-FNA/FNB for operable pancreatic solid mass. Acquire needles (60.4%) were used the most, followed by ProCore needles (47.5%). In terms of need size, most respondents (>80%) preferred 22-gauge needles regardless of the location of the mass. Negative suction with a 10-mL syringe (71.3%) as sampling technique was followed by stylet slow-pull (41.6%). More than three needle passes for EUS-FNA/FNB was performed by most respondents (>80%). The frequency of requiring repeated procedure was significantly higher in respondents with a low individual volume (<5 per month, p=0.001). Prophylactic antibiotics were routinely used in 39 respondents (38.6%); rapid on-site pathologic evaluation was used in 6.1%., Conclusions: According to this survey, practices of EUS-FNA/FNB for pancreatic solid mass varied substantially, some of which differed considerably from the recommendations present in existing guidelines. These results suggest that the development of evidence-based quality guidelines fitting Korean clinical practice is needed to establish the optimal strategy for this procedure.

Background: PTPRF-interacting protein alpha 1 (PPFIA1) plays an important role as a regulator of cell motility and tumor cell invasion and is frequently amplified in breast cancer. The aim of this study was to investigate the clinicopathologic features, survival, anticancer immunities and specific gene sets related to high PPFIA1 expression in patients with breast cancer. We verified the importance of PPFIA1 and survival rates using machine learning and identified drugs that can effectively reduce breast cancer cells with high PPFIA1 expression., Methods: This study analyzed clinicopathologic factors, survival rates, immune profiles and gene sets according to PPFIA1 expression in 3457 patients with breast cancer from the Kangbuk Samsung Medical Center cohort (456 cases), Molecular Taxonomy of Breast Cancer International Consortium (1904 cases) and The Cancer Genome Atlas (1097 cases). We applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analyses, in vitro drug screening, and gradient boosting machine (GBM) analysis., Results: High PPFIA1 expression in breast cancer was associated with worse prognosis, with reduced tumor-infiltrating lymphocytes, especially CD8+ T cells, and increased PD-L1 expression. In pathway network analysis, PPFIA1 was linked directly to the tyrosine-protein phosphatase pathway and indirectly to immune pathways. The importance of PPFIA1's association with survival in GBM analysis was higher than that of perineural and lymphovascular invasion. In in vitro drug screening, expression of PPFIA1 on mRNA level positively correlated with sensitivity of cell lines to erlotinib., Conclusion: High PPFIA1 in patients with breast cancer is related to poor prognosis and decreased anticancer immune response, and erlotinib may be promising for development of therapeutic approaches in patients with tumors overexpressing PPFIA1., (© 2022. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Background: Oral frailty is defined as a slight decline in comprehensive oral function and can predict the onset of adverse health outcomes including morbidity in community-dwelling older adults. Previously, the number of remaining teeth and masticatory status had been suggested to be associated with cognitive decline. The effects of comprehensive oral condition on cognitive decline have not been adequately examined. In this study, we aimed to examine whether oral frailty is associated with new-onset mild cognitive impairment (MCI) among community-dwelling older adults., Methods: Two thousand and forty-four participants of a longitudinal cohort study in Kashiwa City, Chiba Prefecture, without cognitive decline who participated in at least one follow-up survey, were included. New-onset MCI was assessed using the Mini-Mental State Examination (score < 27 defined as MCI). Oral frailty was evaluated based on six components including the number of remaining teeth, masticatory status, tongue pressure, oral motor skills, and subjective difficulties in eating and swallowing. "Oral non-frailty" was defined as good performance on all six measures, "oral pre-frailty" was defined as poor performance on one or two measures, and "oral frailty" was defined as poor performance on three or more measures. Statistical analysis was performed, mainly using a Cox proportional hazards model., Results: Of the 1410 participants who did not fit the exclusion criteria (mean 72.4 ± 5.2 years; 49 % female), 19 % had new-onset MCI during the follow-up period. When comparing the status of oral frailty (non-frailty, oral pre-frailty, and oral frailty), the oral frailty group had a significantly higher hazard ratio for new-onset MCI than the other groups, even after adjusting for confounding factors. Among the six components, a decrease in the number of remaining teeth, low tongue pressure, and difficulty eating tough foods significantly correlated with new-onset MCI. Additionally, we found individuals with co-existing oral frailty and physical frailty to be associated with an increased risk of MCI. However, no significant increase in hazard ratio was observed in participants with either physical or oral frailty., Conclusions: The study findings suggest that oral frailty could predict the risk of new-onset MCI in community-dwelling older adults. Further, we found that oral frailty with physical frailty exacerbated this risk, implying the existence of direct or additive effects on cognitive dysfunction. Comprehensive oral health focusing on maintaining eating function can be a strategy to prevent MCI and delay dementia in community-dwelling older adults., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To establish age- and sex-specific population reference values for tongue pressure (TP) in community-dwelling Japanese older adults., Methods: For this analysis, we pooled four population-based studies on community-dwelling adults aged ≥65 years that measured TP using a JMS tongue pressure measuring device. We calculated the means and deciles of TP per 5-year age group for each sex. We also estimated age trends in TP for men and women., Results: In total, 5,083 individuals (2,150 men and 2,933 women, with a mean [standard deviation] age of 75.2 [6.5] years) were included in the present analysis. In male participants, the mean (standard deviation) TPs for ages 65-69, 70-74, 75-79, 80-84, and ≥85 years were 34.0 (8.4), 32.2 (8.1), 30.8 (8.3), 28.4 (8.9), and 24.4 (8.2) kPa, respectively. In female participants, the corresponding values were 31.5 (7.1), 30.5 (7.5), 29.6 (7.3), 28.4 (8.0), and 26.4 (7.6) kPa, respectively. For both sexes, there were significant declining trends in TP with advanced age. In addition, the interaction between age and sex had a significant effect on TP (regression coefficient [95% confidence interval] = -0.18 [-0.25 to -0.11] when age was modeled as a continuous variable and sex was modeled as a categorical variable [coded as 0=women, 1=men])., Conclusions: This study determined age- and sex-specific reference values for TP, presented as means and deciles, in community-dwelling Japanese older adults aged ≥65 years. This study also demonstrated sex differences in age-related declines in TP.

Background: Prolonged self-restraining behaviors induced by the coronavirus disease 2019 (COVID-19) pandemic's containment measures can limit various positive health behaviors., Objective: We examined the decline in going-out and certain other positive health behaviors and investigated the relationship between excessive decreases in going-out frequency and declining engagement in positive health behaviors among community-dwelling older adults during the self-restraint period., Design: This study employed a cross-sectional survey design., Setting: This study was conducted in Nishi Tokyo City, Tokyo, Japan., Participants: The participants were 294 respondents (150 women) aged 50 years and older who lived in public housing that were permitted to be surveyed during the self-restraint period., Measurements: Their pre-pandemic going-out frequency around February 2020 and going-out frequency during the self-restraint period starting in April 2020 were reported. We mainly assessed the existence of home health behaviors (i.e., exercise, in-person and phone conversations, and healthy diet). A self-report questionnaire was used to obtain data., Results: Going-out frequency decreased in 41.2% of the 294 respondents owing to the government's request for self-restraint. In total, 13 individuals had been going out less than one time per week (housebound) before the request. Of the 281 people who were not housebound before the government's self-restraint request, 13.9% were newly housebound. Newly housebound individuals were 5.3 times less likely to exercise, had 2.1 times fewer social contacts, and 2.6 times less balanced or healthy diets than those who maintained their frequency of going out., Conclusions: Prolonged self-restraint due to the COVID-19 pandemic may lead to housebound status and poor health behaviors. Public health intervention is needed to prevent excessive self-restraint, along with new measures integrating information and communication technologies to enable older adults to live active lives., Competing Interests: Declaration of conflict of interest by Tomoki Tanaka: none; Declaration of conflict of interest by Bo-Kyung Son: none; Declaration of conflict of interest by Katsuya Iijima: none.

Fluoroscopy is used frequently during endoscopic procedures, such as endoscopic retrograde cholangiopancreatography (ERCP). However, exposure to radiation is an important health concern, primarily because of the potential increase in the lifetime risk of malignancy. This consideration is important for patients and staff exposed to radiation during ERCP. Thus, an understanding of how radiation doses are measured during ERCP and the potential risks of this radiation is important. Additionally, staff must be educated about methods used to minimize the radiation dose, such as the use of different imaging techniques, the general principles of fluoroscopy, and advances in hardware and software. The use of personal protective equipment is also essential to minimize occupational exposure. However, no comprehensive ERCP guideline on the use of X-ray systems in clinical settings or on radiation protection for operators has been established. This review focuses on the properties of fluoroscopy systems and methods of radiation protection for physicians and assistants participating in ERCP.

Background/aims: Helicobacter pylori ( H. pylori ) infection highly correlates with erythematous/exudative gastritis, which is one of the endoscopic findings of the Sydney classification system. The present study aimed to evaluate the association between endoscopic severity of erythematous/exudative gastritis and H. pylori infection., Methods: We prospectively enrolled asymptomatic adults who were diagnosed with erythematous/exudative gastritis during screening esophagogastroduodenoscopy. A rapid urease test was performed in all participants to diagnose H. pylori infection. The severity of erythematous/exudative gastritis was determined based on the Sydney classification system. Two investigators independently evaluated the endoscopic findings. The primary endpoint was H. pylori infection rate according to the severity of erythematous/exudative gastritis (mild vs. moderate-to-severe)., Results: A total of 177 patients with erythematous/exudative gastritis were included. The rate of H. pylori infection was 86.4% in all patients. Of 177 included patients, 78 were at mild degree, 48 were at moderate degree, and 51 were at severe degree. The inter-observer variation was 4.6% and kappa value was 0.593. H. pylori infection rate was similar between patients with mild erythematous/exudative gastritis and those with moderate-to-severe erythematous/exudative gastritis (91.0% vs. 82.8%, p=0.115). Even after adjusting potential confounding variables, the severity of erythematous/exudative gastritis was not associated with H. pylori infection rate., Conclusions: H. pylori infection is commonly observed in patients with erythematous/exudative gastritis. However, the severity of erythematous/exudative gastritis is not associated with H. pylori infection rate.

Background/aims: Endoscopic channels are difficult to clean and can cause infection transmission. We examined the effectiveness of a newly developed channel-cleaning ball brush (BB), which is sucked into the endoscopic channel and scrapes and cleans the lumen as it passes through., Methods: The upper and lower gastrointestinal endoscopes used for patient examinations were randomly selected as the conventional brush (CB) or BB group. After manual cleaning, the presence or absence of carbohydrates, proteins, adenosine triphosphate, and hemoglobin was assessed., Results: Fifty-six and 58 endoscopes were cleaned with the CB and BB, respectively. Carbohydrate and protein were detected in one (1.8%) and two endoscopes (3.4%) in the CB and BB groups, respectively (p=1.000). Hemoglobin was observed in one (1.8%) and three endoscopes (5.2%) in the CB and BB groups, respectively (p=0.636). The adenosine triphosphate levels were 10.6±15.9 and 12.5±14.3 relative light units in the CB and BB groups, respectively (p=0.496). Twenty-seven (48.2%) and 19 (32.8%) endoscopes were positive for microbial cultures in the CB and BB groups, respectively (p=0.136)., Conclusion: The efficacy of BB was not significantly different from that of CB in the endoscopic channel-cleaning process.

Purpose: To investigate the cross-sectional associations of nutrition-related, physical, and social factors and their combinations with frailty in community-dwelling older adults., Methods: The participants in this study were 1,161 adults (≥ 65 years). The outcome was frailty severity as assessed by the Cardiovascular Health Study index (score 0: no-frailty, score 1-2: pre-frailty, score ≥ 3: frailty). The independent variables included nutrition-related factors comprising a balanced diet and oral functions, physical factors including exercise habits and awareness of physical function, and social factors including social organizational participation, social support, and social networks. According to the quantity of factors the participants met, four groups were divided. An ordinal logistic regression analysis was conducted to evaluate the associations between frailty severity and the three factors individually and comprehensively., Results: The mean age was 74.6 (±5.4) and the women is 47.8%. 47.7% and 8.7% of participants had pre-frailty or frailty respectively. Meeting no nutrition-related, physical, or social factors individually showed significantly associated with greater adjusted odds ratio (aORs) of frailty severity [aORs (95% confidence interval)]: nutrition-related factors: 1.58 [1.25-2.01]; physical factors: 2.53 [1.98-3.22]; social factors: 1.52 [1.19-1.93]. Referred to participants who met three factors, participants who met two, one, or none showed significantly associated with increased aORs of frailty severity: two: 1.88 [1.34-2.65]; one: 2.97 [2.09-4.23]; none: 7.52 [4.87-11.62]., Conclusion: Meeting no nutrition-related, physical, or social factors individually showed higher risk of being (pre-)frailty. Meeting three factors showed lowest risk of being (pre-)frailty and this risk increased with the quantity decreasing of met factors., (Copyright © 2022. Published by Elsevier B.V.)

Background: Sarcopenia is a major cause of frailty, which relates to nutrition-related, physical, and social factors. In this study, we aimed to discuss the cross-sectional association of sarcopenia with the above three factors both individually and comprehensively., Methods: Overall, 1257 older adults (≥65 years old) participated in this study. Sarcopenia was determined via the Asian Working Group for Sarcopenia 2019 criteria. The independent variables for nutrition-related, physical, and social factors and especially their criteria for health condition were defined separately. Binomial logistic regression analysis was carried out to testify the associations of sarcopenia with three factors individually and in combination., Results: The mean age was 74.6 (±5.5), and women were 47.7%. Sarcopenia prevalence was 7.5%. Participants who did not meet the criteria of nutritional health, physical fitness, or social robustness independently had significant associations with a higher adjusted odds ratio (aOR) of sarcopenia or its indices of lower grip strength, muscle mass, or gait speed. In comparison to participants meeting three criteria, those who met two, one, or none showed (marginally) significant association with increased aOR for sarcopenia (aOR (95% confidence interval)): two: 1.97 (0.84-4.64); one: 2.35 (1.00-5.23); none: 5.52 (2.30-13.23)., Conclusions: Comprehensive countermeasures with the above three factors are indispensable for sarcopenia prevention.

Background/aims: We examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication., Methods: A randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)- based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori . The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases., Results: In total, 350 H. pylori -positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences., Conclusions: TPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier NCT03317223).

Aim: How older adults develop sarcopenia in the community setting is unclear. Focusing on social engagement, we aimed to validate our hypothesized model of sarcopenia development with various contributing factors, such as physical activity, oral function, psychological status and nutritional status. We also clarified direct and indirect effects of social engagement, physical activity, nutritional status, oral function and psychological status on new-onset sarcopenia., Methods: We analyzed 1483 participants' (72.6 ± 5.4 years) longitudinal data from the Kashiwa study. Sarcopenia was assessed in all the surveys in the Kashiwa study. Measures regarding social engagement, physical activity, oral function, psychological status and nutritional status were assessed at baseline. Structural equation modeling was used to analyze the efficiency of the hypothesized model, and calculate direct and indirect effects of factors affecting new-onset sarcopenia., Results: Over the follow-up period (median 6 years [interquartile range 4-6 years]), 12% of individuals developed new-onset sarcopenia. Our structural hypothesis model starting from social engagement to new-onset sarcopenia was suitable (root mean square error of approximation = 0.031, goodness-of-fit index = 0.967, adjusted goodness-of-fit index = 0.954, comparative fix index = 0.911, parsimonious comparative fit index = 0.755; all paths were significant), showing direct effects of social engagement on psychological status, physical activity and oral function, and indirect effects on nutritional status through oral function and psychological status., Conclusions: The present results showed that social engagement could potentially decrease new-onset sarcopenia risks by influencing multidimensional factors, such as physical activity, oral function, and psychological and nutritional status. To prevent sarcopenia, it might be essential to promote social engagement through populational approaches. Geriatr Gerontol Int 2022; 22: 384-391., (© 2022 Japan Geriatrics Society.)

Background: Dementia and frailty often accompany one another in older age, requiring complex care and resources. Available projections provide little information on their joint impact on future health-care need from different segments of society and the associated costs. Using a newly developed microsimulation model, we forecast this situation in Japan as its population ages and decreases in size., Methods: In this microsimulation modelling study, we built a model that simulates an individual's status transition across 11 chronic diseases (including diabetes, coronary heart disease, and stroke) as well as depression, functional status, and self-reported health, by age, sex, and educational strata (less than high school, high school, and college and higher), on the basis of nationally representative health surveys and existing cohort studies. Using the simulation results, we projected the prevalence of dementia and frailty, life expectancy with these conditions, and the economic cost for formal and informal care over the period 2016-43 in the population of Japan aged 60 years and older., Findings: Between 2016 and 2043, life expectancy at age 65 years will increase from 23·7 years to 24·9 years in women and from 18·7 years to 19·9 years in men. Years spent with dementia will decrease from 4·7 to 3·9 years in women and 2·2 to 1·4 years in men. By contrast, years spent with frailty will increase from 3·7 to 4·0 years for women and 1·9 to 2·1 for men, and across all educational groups. By 2043, approximately 29% of women aged 75 years and older with a less than high school education are estimated to have both dementia and frailty, and so will require complex care. The expected need for health care and formal long-term care is anticipated to reach costs of US$125 billion for dementia and $97 billion for frailty per annum in 2043 for the country., Interpretation: Japan's Government and policy makers should consider the potential social challenges in caring for a sizable population of older people with frailty and dementia, and a widening disparity in the burden of those conditions by sex and by educational status. The future burden of dementia and frailty should be countered not only by curative and preventive technology innovation, but also by social policies to mitigate the health gap., Funding: Japan Society for the Promotion of Science, Hitachi - the University of Tokyo Laboratory for a sustainable society, and the National Institute of Ageing., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Functional ability, or the ability to live actively in older age, is essential for healthy ageing. This study assessed the association between the five types of lower urinary tract symptoms (LUTS) and functional ability among community-dwelling older adults (≥65 years old)., Design: A cross-sectional study., Setting: Community-dwelling older adults (≥65 years old) randomly selected from the basic resident register of Kashiwa city as part of the Kashiwa study., Participants: The study included 916 community-dwelling older adults (481 male participants) in Japan., Outcome Measures: A self-administered questionnaire was used to collect data regarding LUTS, which included frequency, nocturia, urgency, urinary incontinence and overactive bladder (OAB). Functional ability was measured using the Japan Science and Technology Agency Index of Competence. Sex-stratified logistic regression analyses were conducted, adjusting age, obesity, alcohol consumption, polypharmacy and comorbidities., Results: Male participants experienced symptoms of frequency, nocturia, urgency, urinary incontinence and OAB at rates of 68.0%, 89.0%, 16.0%, 3.7% and 4.3%, respectively. Female participants experienced these symptoms at rates of 68.3%, 80.0%, 11.0%, 7.4% and 8.5%, respectively. Among male participants, lower functional ability was only associated with nocturia (≥3 times/night) (adjusted OR (AOR): 1.71, 95% CI 1.05 to 2.79). Contrarily, lower functional ability among female participants was significantly associated with frequency (AOR: 1.61, 95% CI 1.04 to 2.49), urgency (AOR: 2.06, 95% CI 1.08 to 3.95) and OAB (AOR: 2.43, 95% CI 1.15 to 5.11)., Conclusion: The different associations between LUTS and functional ability by sex might be related to differences in the effect of comorbidities and physical fatigue. Our results help clarify the multifaceted effects of LUTS in old age, the need for early detection and treatment of LUTS, and the importance of maintaining functional ability., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study aims to investigate the prognostic role of the neutrophil-to-lymphocyte ratio (NLR) in pancreatic neuroendocrine tumors (PNETs) using meta-analysis. This study evaluates the correlation between the NLR and the prognosis in PNETs from nine eligible studies. In addition, a subgroup analysis based on the tumor grade, treatment, and evaluation criteria, was conducted. The estimated rate of a high NLR was 0.253 (95% confidence interval (CI) 0.198-0.317). The rate of high NLRs was significantly lower in patients with lower tumor grades (G1) than those with higher tumor grades (G2 or G3). In addition, the mean value of the NLR was significantly lower in lower tumor grades than in higher tumor grades. High NLRs were significantly correlated with worse overall and recurrence-free survivals (hazard ratio (HR) 2.180, 95% CI 1.499-3.169 and HR 2.462, 95% CI 1.677-3.615, respectively). In a subgroup analysis, the prognostic implications of the NLR were found in both higher and lower criteria of a high NLR. Taken together, our results show that the NLR could be useful for predicting the tumor grade and the prognosis in PNETs.

Background/aims: The study aimed to investigate the current practice patterns in the management of pancreatic cystic neoplasms in Korea., Methods: An electronic survey was systematically distributed by email to members of the Korean Pancreatobiliary Association from December 2019 to February 2020., Results: In total, 115 (110 gastroenterologists, five surgeons) completed the survey, 72.2% of whom worked in a tertiary/academic medical center. Most (65.2%) followed the 2012/2017 International Association of Pancreatology guidelines for the management of pancreatic cystic neoplasms. A gadolinium-enhanced magnetic resonance imaging/magnetic resonance cholangiopancreatography was the most common first-line diagnostic modality (42.1%), but a contrast-enhanced computed tomography scan was preferred as a subsequent surveillance tool (58.3%). Seventy-four percent of respondents routinely performed endoscopic ultrasound-guided fine needle aspiration for pancreatic cystic neoplasms with suspicious mural nodules. Endoscopic ultrasound-guided fine needle aspiration cytology (94.8%) and cystic fluid carcinoembryonic antigen (95.7%) were used for cystic fluid analysis. Most (94%) typically recommended surgery in patients with high-risk stigmata, but 18.3% also considered proceeding with surgery in patients with worrisome features. Most (96.5%) would continue surveillance of pancreatic cystic neoplasms for more than 5 years., Conclusion: According to this survey, there was variability in the management of pancreatic cystic neoplasms among the respondents. These results suggest that the development of evidence-based guidelines for pancreatic cystic neoplasms that fit the Korean practice is needed to create an optimal approach to the management of pancreatic cystic neoplasms.

Social detachment due to coronavirus disease (COVID-19) has caused a decline in physical activity, leading to sarcopenia and frailty in older adults. This study aimed to compare muscle mass, strength, and function values in older women before and after the first wave of the COVID-19 pandemic (April-May 2020). Furthermore, changes in muscle measures across women who experienced different levels of impact on their social participation due to the COVID-19 pandemic were examined. Muscle mass (total, trunk, and appendicular muscle), grip strength, oral motor skills, social interactions (social network and participation), and social support were assessed in 46 Japanese community-dwelling older women (mean, 77.5 y; range 66-93 y) before and after the first wave of the COVID-19 pandemic. Trunk muscle mass significantly decreased after the first wave of the pandemic. When comparing changed values between the enhanced/maintained and reduced group during the pandemic, significant group difference was observed in trunk muscular mass, grip strength, and oral motor skills. Intriguingly, those who enhanced social participation had a positive change of grip strength values, showing that social participation might influence muscle function during the COVID-19 pandemic., Competing Interests: All authors declare that they have no conflicts of interest.

Health literacy (HL) promotes healthy lifestyle behaviors among older adults, and its relationship with frailty remains unclear. This study examined whether HL is a predictor of frailty progression among community-dwelling older adults. Data from two surveys conducted in 2012 and 2016 involving older residents (mean age, 71.6 ± 4.6 years) of Kashiwa City, Chiba Prefecture, Japan were used. Only healthy individuals without frailty and cognitive impairments participated in the 2012 assessment, where the Kihon Checklist (KCL), HL, and other variables were assessed. Logistic and multiple logistic analyses were used to assess the effects of HL and other factors on frailty between the 'high HL' vs. 'low HL' groups in 2012 and between the 'robust' vs. 'frailty-progressing' groups in 2016. Of the 621 robust participants, 154 (25.4%) had progression of frailty in 2016, which was significantly associated with advanced age, higher KCL score, lower HL, poor mental health, and lack of social support. Furthermore, low HL was a predictor of frailty progression. Low HL may be associated with frailty progression. The obtained results suggest that increased health literacy should be effective in preventing frailty for community-dwelling older residents.

Background/aims: The work environment in which endoscopic retrograde cholangiopancreatography (ERCP) is conducted has influence on its efficacy and safety. We aimed to assess the current status of ERCP work environments and to investigate the trends associated with the basic techniques of ERCP in Korea., Methods: The work environment and information on the basic techniques of ERCP were acquired by the Korean Pancreatobiliary Association (KPBA) through a national survey in 2019. The survey was performed at the KPBA conference in 2019. The contents of survey comprised of the current environment of ERCP, preparation before ERCP, and the preferred basic techniques used in ERCP., Results: Completed questionnaires were returned from 84 KPBA members. The mean ERCP volume per year was approximately 500. About 60% (50/84) reported that they worked with a dedicated ERCP team with experienced nurses. Two-thirds (57/84, 68%) answered that they had a fluoroscopy room used solely for ERCP procedures. All respondents intravenously hydrated the patient to prevent post-ERCP pancreatitis (84/84, 100%). The preferred procedural sedations were balanced propofol sedation (50%) and midazolam-only sedation (47%). Wire-guided cannulation was most commonly used for selective cannulation (81%). Endoscopic retrograde biliary drainage was preferred over endoscopic nasobiliary drainage (60% vs 22%). The initial method of ampullary intervention was endoscopic sphincterotomy in 60%., Conclusions: Data from the survey involving a large number of Korean ERCP doctors revealed considerable variabilities with regard to the work environment and basic techniques of ERCP in Korea. The study provides information regarding the current trends of ERCP that can be used to establish ERCP standards in Korea.

Purpose: Chronic inflammation is a pathophysiological cause of age-related diseases including sarcopenia. However, limited data are available on the association between the diet-derived inflammation and sarcopenia. Here, using the Dietary Inflammatory Index (DII), we examined the associations between inflammatory potentials of the diet, sarcopenia/its components, and serum inflammatory markers., Materials and Methods: This cross-sectional study was performed in 2014 among 1,254 community-dwelling older adults. Energy-adjusted DII score (E-adjusted DII) was calculated using a self-administered diet history questionnaire. Sarcopenia/its components was determined according to the Asian Working Group for Sarcopenia. Serum interleukin (IL)-1β, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)α, and high-sensitivity C-reactive protein (hsCRP) were measured., Results: The mean of E-adjusted DII was 0.13±2.1 (-4.92~5.29) in participants (74.6±5.5 y). After adjustment of confounders, men in the highest tertile of the E-adjusted DII showed a 2.89-times (95% CI: 1.04-8.04) higher risk of sarcopenia than those in the lowest tertile. Regarding its components (low muscle mass/strength/function), men in the highest tertile did not have significantly greater odds, respectively. Intriguingly, when the E-adjusted DII was calculated only based on anti-inflammatory food parameters, men who did not consume food with anti-inflammatory properties scored high E-adjusted DII and were significantly associated with sarcopenia in the highest tertile (OR: 2.96; 95% CI: 1.06-8.93). Higher serum hsCRP levels were seen in sarcopenic men with the highest E-adjusted DII (p=0.036)., Conclusions: These results suggest that a diet with pro-inflammatory potential is associated with the risk of sarcopenia. Further investigations whether anti-inflammatory diet could reduce its risk are needed., (Copyright © 2021. Published by Elsevier B.V.)