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Objectives: Radial incision and cutting (RIC) is being investigated as an alternative endoscopic dilation method for lower intestinal tract stenosis, providing a high technical success rate and improving subjective symptoms. However, several patients develop re-stenosis following RIC. In this pilot study, we aimed to evaluate the safety and efficacy of triamcinolone acetonide (TA) addition after RIC., Methods: RIC with TA was performed in 20 patients with lower gastrointestinal tract stenosis. We evaluated the rate of adverse events 2 months after RIC with TA. We investigated the short- and long-term prognoses, as well as the improvement in subjective symptoms, using a visual analog scale., Results: The delayed bleeding rate after RIC was 23.8%. Endoscopic hemostasis was achieved in all patients with delayed bleeding. No perforations were observed. The cumulative re-stenosis-free, re-intervention-free, and surgery-free rates 1 year after RIC were 52.9%, 63.7%, and 85.2%, respectively. Subjective symptoms, including abdominal pain, abdominal bloating, nausea, and dyschezia, significantly improved after RIC with TA., Conclusion: Although additional TA administration after RIC could be safe, additional TA may not be effective on luminal patency after dilation. Further investigation is warranted., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Mutations in the epidermal growth factor receptor (EGFR) gene are the most common targetable gene alterations in non-small cell lung cancer (NSCLC). In Japan, approximately 40% of patients who undergo surgical resection for non-squamous NSCLC have EGFR mutations. However, no long-term studies have been conducted including a large number of EGFR-positive NSCLC patients with postoperative recurrence (PR)., Methods: We conducted a retrospective observational study of the data of EGFR-positive NSCLC patients with PR who had undergone surgery at the Shizuoka Cancer Center between October 2002 and November 2017. We evaluated post-recurrence overall survival (PRS) and postoperative overall survival (POS) using the Kaplan-Meier method and identify any associations between the clinical variables at recurrence and PRS using univariate and multivariate analysis., Results: We enrolled 162 patients. The median observation time for PRS was 4.95 years (range, 0.82-13.25) and POS was 5.81 years (range, 2.84-16.71). The median PRS was 5.17 years (95% confidence interval [CI], 3.90-5.61) and POS was 7.07 years (95% CI, 5.88-8.01). Univariate analysis identified male sex (median PRS: 3.32 vs. 5.39 years; p < 0.05), bone metastasis (median PRS: 2.43 vs. 5.33 years; p < 0.05), and central nervous system (CNS) metastasis (median PRS: 3.05 vs. 5.39 years; p < 0.05) and multivariate analysis identified bone metastasis (hazard ratio [HR], 2.01; 95% CI, 1.23-3.28; p < 0.05) and CNS metastasis (HR, 1.84; 95% CI, 1.14-2.98; p < 0.05) as poor prognostic factors. The pattern of recurrence (oligo vs. non-oligo recurrence) was not a prognostic factor. Logistic regression analysis revealed the association between sex and the presence bone/CNS metastasis at recurrence., Conclusion: Our data may help visualize future prospects and determine the timing of osimertinib initiation. New treatment strategies need to be developed for patients with bone/CNS metastasis at the first recurrence., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Background: Chemotherapy-induced anorexia is a common occurrence in patients undergoing treatment for advanced lung cancer. However, the relationship between chemotherapy-induced anorexia and weight loss during platinum-based chemotherapy combined with immune checkpoint inhibitors is unclear. This study explored the relationship between chemotherapy-induced anorexia and therapeutic outcomes in patients with stage IV non-small-cell lung cancer undergoing platinum-based chemotherapy combined with immune checkpoint inhibitors., Methods: The study retrospectively reviewed the medical records of 106 patients with stage IV non-small-cell lung cancer treated with platinum-based chemotherapy and immune checkpoint inhibitors between January 2019 and October 2022. The incidence of weight loss and its association with treatment efficacy was assessed in the chemotherapy-induced anorexia group. Chemotherapy-induced anorexia, nausea, and vomiting were evaluated using Common Terminology Criteria for Adverse Events v 5.0. Progression-free and overall survival were used to measure treatment efficacy., Results: Chemotherapy-induced anorexia was observed in 13.2% of patients. These patients exhibited significant weight loss at 6 and 9 weeks after treatment initiation compared to those in the non-chemotherapy-induced anorexia group. Progression-free and overall survival were shorter in the chemotherapy-induced anorexia group than in the non-chemotherapy-induced anorexia group, but the difference was not statistically significant., Conclusions: Chemotherapy-induced anorexia was associated with significant weight loss and reduced treatment efficacy in patients with stage IV non-small-cell lung cancer. These results highlight the importance of implementing robust supportive care for chemotherapy-induced anorexia to mitigate weight loss and uphold treatment effectiveness during platinum-based chemotherapy combined with immune checkpoint inhibitors., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Introduction: The effect of polypharmacy on older patients with cancer is unclear. This study aimed to explore the effect of polypharmacy on the outcomes of treatment in older patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors., Materials and Methods: We retrospectively reviewed the records of older patients (aged ≥65 years) with advanced NSCLC who received PD-1/PD-L1 inhibitors with or without platinum-based chemotherapy as first-line treatment from March 2016 to December 2020. Patients with driver oncogenes or Eastern Cooperative Oncology Group performance status (PS) ≥2 were excluded. Polypharmacy was defined as receiving five or more oral or inhaled medications at baseline. We compared the progression-free survival (PFS), overall survival (OS), and mean cumulative length of hospital stays between the polypharmacy and non-polypharmacy groups., Results: A total of 122 patients, with a median age of 72 years (range, 65-89 years), were included in the analysis. Of the patients, 34 (27.8%) had a PS of 0 and 68 (55.7%) had a PD-L1 tumor proportion score (TPS) of ≥50%. The median number of oral or inhaled medications was 4 (range, 0-12), and 60 (49.1%) patients were taking ≥5 medications (polypharmacy). Age and Charlson Comorbidity Index score were significantly higher in the polypharmacy group (P = 0.01 and P < 0.001, respectively). Compared with the non-polypharmacy group, the polypharmacy group had a similar median PFS (6.7 vs. 8.5 months, P = 0.94) and a shorter median OS (17.3 vs. 26.0 months, P = 0.04). In the polypharmacy group, the adjusted hazard ratio for OS (adjusted for age, PS, and PD-L1 TPS) was 1.65 (95% confidence interval, 1.04-2.86, P = 0.03). Patients in the polypharmacy group had longer hospital stays (46.3 ± 7.5 vs. 27.7 ± 4.1 days/person, P < 0.05) and more emergency hospitalizations (1.6 ± 0.3 vs. 0.8 ± 0.1 times/person, P < 0.05) during the first year., Discussion: Polypharmacy was associated with shorter survival time and longer hospitalization in older patients with advanced NSCLC receiving first-line immunotherapy with or without chemotherapy., Competing Interests: Declaration of Competing Interest None of the authors has any financial or personal relationships with other individuals or organizations that could inappropriately influence this study., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: We devised a method that combines the 3D-Dixon-gradientecho (GRE) method with an improved motion-sensitized driven-equilibrium (iMSDE) to suppress blood flow signals., Purpose: The purpose of this study was to evaluate the effectiveness of the new method we developed plaque imaging method (3D-Dixon-GRE with the iMSDE method)., Study Type: Retrospective cohort., Population: Thirty-nine patients who underwent cervical plaque imaging., Field Strength/sequence: 3.0 T/3D-GRE., Assessment: Signal intensities of the common carotid artery, aorta, plaque, muscle, and subcutaneous fat were measured through the VISTA and the 3D-Dixon-GRE with iMSDE methods, and each contrast was calculated., Statistical Test: Used the Mann Whitney U test. P-values below 0.05 were considered statistically significant., Results: Plaque and muscle contrast estimated through the VISTA method and 3D-Dixon-GRE with iMSDE method was 1.60 ± 0.96 and 2.04 ± 1.06, respectively, (P < 0.05). The contrast between the flow (common carotid artery and Aorta) and muscle according to the VISTA method and 3D-Dixon-GRE with iMSDE method was 0.24 ± 0.11 and 0.40 ± 0.12, respectively (P < 0.001). Finally, the mean contrast for subcutaneous fat and muscle at six locations was 3.05 ± 1.25 and 0.81 ± 0.23 for the VISTA method and 3D-Dixon-GRE with the iMSDE method, respectively (P < 0.001)., Data Conclusion: Compared to the conventional method (VISTA), the 3D-Dixon-GRE with iMSDE method is preferable in relation to the fat suppression effect, but it is disadvantageous regarding blood flow signal suppression. Therefore, the 3D-Dixon-GRE with the iMSDE method could be considered useful for plaque imaging., Competing Interests: Declaration of competing interest No conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Recent advent of diverse chemical entities necessitates a re-evaluation of chemical bond concepts, underscoring the importance of experimental evidence. Our prior study introduced a general methodology, termed Core Differential Fourier Synthesis (CDFS), for mapping the distribution of valence electron density (VED) in crystalline substances within real space. In this study, we directly compare the VED distributions obtained through CDFS with those derived from high-accuracy theoretical calculation using long-range corrected density functional theory, which quantitatively reproduces accurate orbital energies. This comparison serves to demonstrate the precision of the CDFS in replicating complex details. The VED patterns observed experimentally exhibited detailed structures and phases of wave functions indicative of sp 3 hybrid orbitals, closely aligning with theoretical predictions. This alignment underscores the utility of our approach in gathering quantum chemical data experimentally, a crucial step for discussing the chemical properties, such as reaction mechanisms.

Peribiliary glands are complex lobular structures containing mucus and serous glands, distributed along the extrahepatic and intrahepatic bile ducts. In this report, we describe a case of intraductal papillary neoplasm of the bile duct suspected to be of peribiliary glands origin. The patient was an 80-year-old man who was referred to our hospital for a hepatic mass. On further examination, a 38 × 34 mm cystic lesion with papillary growth was found in S1/4. Because the lesion was extensively bordered by both hepatic ducts and the connection was unclear, it was difficult to determine the extent of hepatic resection. To confirm the location, a peroral cholangioscopy was performed. The connection with the cyst was detected in the right hepatic duct and a villous tumor mucosa protruded through the conduit lumen. Since we found that the lesion communicated with the right hepatic duct, a right hepatectomy was subsequently performed. The postoperative pathological diagnosis was an intraductal papillary neoplasm of the blie duct with associated invasive carcinoma. The postoperative course was good, and the patient experienced no recurrence., Competing Interests: None., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: The clinical application of human induced pluripotent stem cell-derived cardiomyocytes (CMs) for cardiac repair commenced with the epicardial delivery of engineered cardiac tissue; however, the feasibility of the direct delivery of human induced pluripotent stem cell-derived CMs into the cardiac muscle layer, which has reportedly induced electrical integration, is unclear because of concerns about poor engraftment of CMs and posttransplant arrhythmias. Thus, in this study, we prepared purified human induced pluripotent stem cell-derived cardiac spheroids (hiPSC-CSs) and investigated whether their direct injection could regenerate infarcted nonhuman primate hearts., Methods: We performed 2 separate experiments to explore the appropriate number of human induced pluripotent stem cell-derived CMs. In the first experiment, 10 cynomolgus monkeys were subjected to myocardial infarction 2 weeks before transplantation and were designated as recipients of hiPSC-CSs containing 2×10 7 CMs or the vehicle. The animals were euthanized 12 weeks after transplantation for histological analysis, and cardiac function and arrhythmia were monitored during the observational period. In the second study, we repeated the equivalent transplantation study using more CMs (6×10 7 CMs)., Results: Recipients of hiPSC-CSs containing 2×10 7 CMs showed limited CM grafts and transient increases in fractional shortening compared with those of the vehicle (fractional shortening at 4 weeks after transplantation [mean ± SD]: 26.2±2.1%; 19.3±1.8%; P <0.05), with a low incidence of posttransplant arrhythmia. Transplantation of increased dose of CMs resulted in significantly greater engraftment and long-term contractile benefits (fractional shortening at 12 weeks after transplantation: 22.5±1.0%; 16.6±1.1%; P <0.01, left ventricular ejection fraction at 12 weeks after transplantation: 49.0±1.4%; 36.3±2.9%; P <0.01). The incidence of posttransplant arrhythmia slightly increased in recipients of hiPSC-CSs containing 6×10 7 CMs., Conclusions: We demonstrated that direct injection of hiPSC-CSs restores the contractile functions of injured primate hearts with an acceptable risk of posttransplant arrhythmia. Although the mechanism for the functional benefits is not fully elucidated, these findings provide a strong rationale for conducting clinical trials using the equivalent CM products., Competing Interests: S.T. is an advisor to Heartseed Inc. K.F. is the cofounder and CEO of Heartseed Inc. S.T., H. Kanazawa, and K.F. own equity in Heartseed Inc.

Dental caries and periodontal disease are typical oral diseases frequently observed in patients with renal diseases. Tooth loss is an outcome of dental caries and periodontal disease, and the number of existing teeth is an indicator of oral health status. However, the association between the number of existing teeth and end-stage kidney disease (ESKD) has not been investigated in detail. This study aimed to investigate the association between oral health status, expressed by the number of existing teeth, and ESKD. We analyzed data from the second survey of the Longitudinal Evaluation of Multi-phasic, Odontological, and Nutritional Associations in Dentists, a cohort study conducted among members of the Japan Dental Association. From August 2016 to July 2017, self-administered questionnaires were mailed to 16,128 male dentists and 8,722 responded. Among them, 7,479 men with complete data on age, number of existing teeth, and ESKD were included in the analysis. Multivariate logistic regression analysis was conducted, with ESKD as the dependent variable and the number of existing teeth (≥23 teeth and <23 teeth) as the independent variable. Subgroup analysis by age (<65 years and ≥65 years) was also conducted. The <23 teeth group had a significantly higher rate of ESKD than did the ≥23 teeth group. After adjusting for age, body mass index, smoking habits, hypertension, and diabetes mellitus, there was no significant association between having <23 teeth and ESKD in all participants. However, the subgroup analysis revealed a significant association after adjustment for covariates in participants aged <65 years but not in those aged ≥65 years. In conclusion, having <23 teeth was associated with the risk of requiring maintenance dialysis therapy among Japanese men aged <65 years. Therefore, tooth loss may be associated with renal function decline., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kondo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Several X-linked genes escape from X chromosome inactivation (XCI), while differences in escape across cell types and tissues are still poorly characterized. Here, we developed scLinaX for directly quantifying relative gene expression from the inactivated X chromosome with droplet-based single-cell RNA sequencing (scRNA-seq) data. The scLinaX and differentially expressed gene analyses with large-scale blood scRNA-seq datasets consistently identified the stronger escape in lymphocytes than in myeloid cells. An extension of scLinaX to a 10x multiome dataset (scLinaX-multi) suggested a stronger escape in lymphocytes than in myeloid cells at the chromatin-accessibility level. The scLinaX analysis of human multiple-organ scRNA-seq datasets also identified the relatively strong degree of escape from XCI in lymphoid tissues and lymphocytes. Finally, effect size comparisons of genome-wide association studies between sexes suggested the underlying impact of escape on the genotype-phenotype association. Overall, scLinaX and the quantified escape catalog identified the heterogeneity of escape across cell types and tissues., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Evaluating the accuracy and educational utility of artificial intelligence-generated medical cases, especially those produced by large language models such as ChatGPT-4 (developed by OpenAI), is crucial yet underexplored., Objective: This study aimed to assess the educational utility of ChatGPT-4-generated clinical vignettes and their applicability in educational settings., Methods: Using a convergent mixed methods design, a web-based survey was conducted from January 8 to 28, 2024, to evaluate 18 medical cases generated by ChatGPT-4 in Japanese. In the survey, 6 main question items were used to evaluate the quality of the generated clinical vignettes and their educational utility, which are information quality, information accuracy, educational usefulness, clinical match, terminology accuracy (TA), and diagnosis difficulty. Feedback was solicited from physicians specializing in general internal medicine or general medicine and experienced in medical education. Chi-square and Mann-Whitney U tests were performed to identify differences among cases, and linear regression was used to examine trends associated with physicians' experience. Thematic analysis of qualitative feedback was performed to identify areas for improvement and confirm the educational utility of the cases., Results: Of the 73 invited participants, 71 (97%) responded. The respondents, primarily male (64/71, 90%), spanned a broad range of practice years (from 1976 to 2017) and represented diverse hospital sizes throughout Japan. The majority deemed the information quality (mean 0.77, 95% CI 0.75-0.79) and information accuracy (mean 0.68, 95% CI 0.65-0.71) to be satisfactory, with these responses being based on binary data. The average scores assigned were 3.55 (95% CI 3.49-3.60) for educational usefulness, 3.70 (95% CI 3.65-3.75) for clinical match, 3.49 (95% CI 3.44-3.55) for TA, and 2.34 (95% CI 2.28-2.40) for diagnosis difficulty, based on a 5-point Likert scale. Statistical analysis showed significant variability in content quality and relevance across the cases (P<.001 after Bonferroni correction). Participants suggested improvements in generating physical findings, using natural language, and enhancing medical TA. The thematic analysis highlighted the need for clearer documentation, clinical information consistency, content relevance, and patient-centered case presentations., Conclusions: ChatGPT-4-generated medical cases written in Japanese possess considerable potential as resources in medical education, with recognized adequacy in quality and accuracy. Nevertheless, there is a notable need for enhancements in the precision and realism of case details. This study emphasizes ChatGPT-4's value as an adjunctive educational tool in the medical field, requiring expert oversight for optimal application., (©Hiromizu Takahashi, Kiyoshi Shikino, Takeshi Kondo, Akira Komori, Yuji Yamada, Mizue Saita, Toshio Naito. Originally published in JMIR Medical Education (https://mededu.jmir.org), 13.08.2024.)

Background: Observational studies have reported associations between primary aldosteronism (PA) and cardiovascular outcomes, including coronary artery diseases (CAD), congestive heart failure (CHF), and stroke. However, establishing causality remains a challenge due to the lack of randomized controlled trial data on this topic. We thus aimed to investigate the causal relationship between PA and the risk of developing CAD, CHF, and stroke., Methods and Results: Cross-ancestry meta-analysis of genome-wide association studies combining East Asian and European ancestry (1560 PA cases and 742 139 controls) was conducted to identify single-nucleotide variants that are associated with PA. Then, using the identified genetic variants as instrumental variables, we conducted the 2-sample Mendelian randomization analysis to investigate the causal relationship between PA and incident CAD, CHF, and stroke among both East Asian and European ancestry. Summary association results were extracted from large genome-wide association studies consortia. Our cross-ancestry meta-analysis of East Asian and European populations identified 7 genetic loci significantly associated with the risk of PA, for which the genes nearest to the lead variants were CASZ1 , WNT2B , HOTTIP , LSP1 , TBX3 , RXFP2 , and NDP . Among the East Asian population, the pooled odds ratio estimates using these 7 genetic instruments of PA were 1.07 (95% CI, 1.03-1.11) for CAD, 1.10 (95% CI, 1.01-1.20) for CHF, and 1.13 (95% CI, 1.09-1.18) for stroke. The results were consistent among the European population., Conclusions: Our 2-sample Mendelian randomization study revealed that PA had increased risks of CAD, CHF, and stroke. These findings highlight that early and active screening of PA is critical to prevent future cardiovascular events.

Background: Hospitalists may work in a variety of clinical settings to manage COVID-19 cases. However, the extent of their involvement in COVID-19 care is unknown, particularly in hospitals without infectious disease (ID) specialists., Methods: This study aimed to confirm whether hospitalists provided COVID-19 management in various clinical settings when ID specialists were unavailable. We conducted a multicenter cross-sectional study using a web-based questionnaire. The participants were full-time hospitalists working in Japanese academic community-based hospitals. The study period was from 15 January 2021 to 15 February 2021, during Japan's third wave of the COVID-19 pandemic. The primary outcome was the rate of hospitalists participating in COVID-19 inpatient management in hospitals with or without ID specialists., Results: ID specialists were absent in 31% of small hospitals (those with fewer than 249 registered beds), but only 4% of large hospitals ( p  < 0.001). Hospitalists were more likely to manage both COVID-19 inpatient care and emergency department care in hospitals without than with hospitals with ID specialists (76 versus 56% ( p  = 0.01) and 90 versus 73% ( p  = 0.01), respectively). After adjusting for confounders by multivariate analysis, hospitalists who worked in hospitals without ID specialists had higher odds of participating in COVID-19 inpatient care than those who worked in hospitals with such specialists (adjusted odds ratio: 3.0, 95% CI: 1.2-7.4)., Conclusion: Hospitalists were more likely to provide COVID-19 inpatient care in various clinical settings in hospitals without ID specialists.

We herein report a novel de novo KCNH5 variant in a patient with refractory epileptic encephalopathy. The patient exhibited seizures at 1 year and 7 months old, which gradually worsened, leading to a bedridden status. Brain magnetic resonance imaging (MRI) showed cerebral atrophy and cerebellar hypoplasia. A trio whole-exome sequence analysis identified a de novo heterozygous c.640A>C, p.Lys214Gln variant in KCNH5 that was predicted to be deleterious. Recent studies have linked KCNH5 to various epileptic encephalopathies, with many patients showing normal MRI findings. The present case expands the clinical spectrum of the disease, as it is characterized by severe neurological prognosis, cerebral atrophy, and cerebellar hypoplasia.

Background: Anamorelin is a selective ghrelin receptor agonist approved for cancer cachexia in Japan. Little is known about predictors of anamorelin efficacy. This study aimed to assess the effect of diabetes on the efficacy and safety of anamorelin in patients with cancer cachexia., Methods: Medical records of patients with advanced non-small-cell lung, gastric, pancreatic, or colorectal cancer who received anamorelin between January 2021 and March 2023 were retrospectively reviewed. The diabetic (DM) group included patients with a confirmed diagnosis of type 2 diabetes mellitus, random plasma glucose of ≥ 200 mg/dL, or hemoglobin A1c of ≥ 6.5%. The maximum body weight gain and adverse events during anamorelin administration were compared between the DM and non-DM groups. Patients with a maximum body weight gain ≥ 0 kg were classified as the responders., Results: Of 103 eligible patients, 31 (30.1%) were assigned to the DM group. The DM group gained less weight (median of -0.53% vs. + 3.00%, p < 0.01) and had fewer responders (45.2% vs. 81.9%, p < 0.01) than the non-DM group. The odds ratio for non-response in the DM group was 6.55 (95% confidential interval 2.37-18.06, p < 0.01), adjusted by age and performance status. The DM group had a higher cumulative incidence of hyperglycaemic adverse events (72.2% vs. 6.3%, p < 0.01) and more discontinuations due to hyperglycaemic adverse events (25.8% vs. 4.2%, p < 0.01) than the non-DM group., Conclusions: Patients with diabetes and cancer cachexia are less likely to gain weight with anamorelin despite a high risk of hyperglycaemic adverse events., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Aspiration pneumonia has a high recurrence rate, and oral care by dentists has been found effective in preventing its onset; however, this has not been evaluated using prospective studies. Therefore, we conducted a prospective study to evaluate the effectiveness of professional oral care by dentists in reducing aspiration pneumonia recurrence in older adult patients., Methods: In this prospective cohort study, we evaluated a dental oral care intervention, using a historical control group (control group). It was conducted at a single-centre regional core hospital in Japan that serves a large number of patients aged older than 80 years. Patients who were hospitalised for aspiration pneumonia were included in this study. During the study period (1 April 2021 to 31 March 2022), the clinical group received weekly professional cleaning by a dentist and the control group received standard oral care by a nurse as usual from 1 April 2020 to 31 March 2021. The dentist oral care group received weekly professional oral care from a dentist and was followed prospectively for 1 year. A Kaplan-Meier analysis was used to evaluate the timing of recurrent aspiration pneumonia or death. A Cox proportional hazards model was used to obtain a hazard ratio and determine the 95% confidence intervals., Results: There were 91 participants in the clinical group and 94 in the control group. The mean age of participants was 85 years, and 75 (40.5%) were female. The recurrence rate was 27.5% in the clinical group and 44.7% in the control group (P = .005). Professional cleaning by a dentist reduced the risk of recurrence of aspiration pneumonia by approximately 50% (adjusted hazard ratio, 0.465; 95% confidence interval, 0.278-0.78)., Conclusions: Professional cleaning by a dentist was associated with a lower rate of aspiration pneumonia recurrence than nurse-provided conventional oral care., Competing Interests: Conflict of interest None disclosed., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is one of the most common and serious adverse events associated with ERCP. Thus, we aimed to investigate the usefulness of pre-ERCP pancreatic volume, which is deeply involved in exocrine pancreatic function, as a predictor of PEP development and severity., Methods: In total, 1107 patients who underwent their first ERCP were recruited from January 2012 to December 2022 for this retrospective study. Pancreatic volume was measured by cross-sectional analysis using pre-ERCP computed tomography images. The potential risk factors for PEP were analyzed using multivariate logistic regression., Results: Of the 745 patients included in the study, 34 (4.6 %) developed PEP: severe, moderate, or mild PEP in 1, 7, and 26 cases, respectively. Multivariate analysis revealed that only a large pancreatic volume (>70 cm 3 ) was an independent risk factor for the development of PEP (odds ratio, 7.98; 95 % confidence interval, 11.80-67.50; P < 0.001). Additionally, the incidence of PEP was significantly higher in patients with a pancreatic volume >70 cm 3 than in those with a pancreatic volume ≤70 cm 3 (18.5 % [31/168] vs. 0.5 % [3/577]; P < 0.001). Also, the association between the pre-ERCP pancreatic volume and PEP severity was positively correlated (r = 0.625, P < 0.005), with a larger pancreatic volume corresponding to increased PEP severity., Conclusions: A large pancreatic volume before ERCP may be a novel risk factor for PEP incidence and severity. This finding suggests that quantitative analysis of the pre-ERCP pancreatic volume could be a useful predictor of PEP., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Early childhood lays the foundation for many outcomes in later life. Recent studies suggest that early childhood development may contribute to lifestyle-related diseases such as obesity, type 2 diabetes, and cardiovascular disease in adulthood; however, there have been few investigations on this association among adults in Japan. Therefore, we examined the relationship between recent physical measurements in adults who underwent health checkups at our university and their physical measurements at birth and during infancy recorded in the Maternal and Child Health Handbook. The median age and body mass index (BMI) of the participants were 36 years and 20.4 kg/m 2 , respectively. BMI at the time of health checkup in adults did not correlate with physical measurements at birth, but it was found to be associated with BMI at 1.5 (regression coefficient (β) 0.53, p < 0.05) and 3 (β 0.7, p < 0.01) years of age. In addition, the waist-to-height ratio in adulthood was also associated with BMI at 1.5 (β 0.01, p < 0.05) and 3 (β 0.01, p < 0.05) years of age. These findings suggest that it is critical to provide appropriate guidance to children with high BMI and their parents during health checkups to prevent lifestyle-related disorders in adulthood.

Diagnosis improvement requires physician-nurse collaboration. This study explored nurses' concerns regarding physicians' diagnoses and how they were communicated to physicians. This cross-sectional study, employing a web-based questionnaire, included nurses registered on Japan's largest online media site from June 26, 2023, to July 31, 2023. The survey inquired whether participants felt concerned about a physician's diagnosis within a month, if they communicated their concerns once they arose, and, if not, their reasons. The reasons for not being investigated were also examined. The nurses' frequency of feeling concerned about a physician's diagnosis and the barriers to communicating these concerns to the physician were evaluated. Overall, 430 nurses answered the survey (female, 349 [81.2%]; median age, 45 [35-51] years; median years of experience, 19 [12-25]). Of the nurses, 61.2% experienced concerns about a physician's diagnosis within the past month; 52.5% felt concerned but did not communicate this to the physician. The most common reasons for not communicating included concern about the physician's pride, being ignored when communicating, and the nurse not believing that a diagnosis should be made. Our results highlight the need to foster psychologically safe workplaces for nurses and create educational programs encouraging nurse involvement in diagnosis., (© 2024. The Author(s).)

Background and Aim: Although sleep disorders are associated with the pathogenesis of inflammatory bowel disease, the causal relationship is unclear. Therefore, in this study we aimed to clarify the causal relationship between them., Methods: We administered the Pittsburgh Sleep Questionnaire to participants during regular visits to evaluate their sleep condition and prospectively observed the participants. Participants were divided into poor sleep and non-poor sleep groups according to their first and second questionnaire scores. We compared inflammatory bowel disease relapse rates between the two groups., Results: The study population included 139 patients with inflammatory bowel disease, including 60 with chronic poor sleep. Disease relapse rate was significantly higher in the poor sleep group than in the non-poor sleep group (28.3% vs. 8.9%; P=0.0033). Ulcerative colitis relapse rate was significantly higher in the poor sleep group than in the non-poor sleep group (34.5% vs. 10.3%, P=0.031). Multivariate analysis identified chronic poor sleep as a clinical factor that affected inflammatory bowel disease relapse (OR=6.69, 95% CI: 2.23-20.0, P=0.0007) and ulcerative colitis relapse (OR=8.89, 95% CI: 1.57-50.2, P=0.014). The Kaplan-Meier curve showed significantly lower cumulative treatment retention rates in the poor sleep group than in the non-poor sleep group (all patients, P=0.0061; ulcerative colitis, P=0.025)., Conclusions: Concomitant chronic poor sleep may have a negative influence on the disease activity in patients with inflammatory bowel disease, especially in those with ulcerative colitis., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

A lack of adherence to long-term antiretroviral therapy may impact viral suppression. The current study examined the relationship between medication adherence and clinical outcomes in people with human immunodeficiency virus infection (PWH) receiving bictegravir, emtricitabine, and tenofovir alafenamide fumarate (B/F/TAF). A retrospective cohort study using two Japanese claims databases was conducted. Adherence was measured by the proportion of days covered (PDC). Patients were grouped into 3 PDC category and persistence was estimated by Kaplan-Meier method. Cox regression analysis was performed to investigate whether the PDC was associated with treatment discontinuation. Among 952 patients, 820 (86.1%), 95 (10.0%), and 37 (3.9%) patients were grouped into the PDC ≥ 90%, 80- < 90%, and < 80% groups, respectively. Across all PDC groups, more than 90% of patients who received B/F/TAF were receiving treatment at 1 year. There was no significant difference in the risk of discontinuation between the lower PDC groups (80- < 90% and < 80%) and the PDC ≥ 90% group (0.400 [0.096, 1.661]; 2.244 [0.663, 7.594], hazard ratio [95% confidence interval], respectively). A drug resistance test was implemented for 15 patients, none of whom discontinued B/F/TAF after the test. The results suggest that events that could cause discontinuation, such as virologic failure, were not associated with PDC., (© 2024. The Author(s).)

Recurrent pregnancy loss (RPL) is a major reproductive health issue with multifactorial causes, affecting 2.6% of all pregnancies worldwide. Nearly half of the RPL cases lack clinically identifiable causes (e.g., antiphospholipid syndrome, uterine anomalies, and parental chromosomal abnormalities), referred to as unexplained RPL (uRPL). Here, we perform a genome-wide association study focusing on uRPL in 1,728 cases and 24,315 female controls of Japanese ancestry. We detect significant associations in the major histocompatibility complex (MHC) region at 6p21 (lead variant=rs9263738; P = 1.4 × 10 -10 ; odds ratio [OR] = 1.51 [95% CI: 1.33-1.72]; risk allele frequency = 0.871). The MHC associations are fine-mapped to the classical HLA alleles, HLA-C*12:02, HLA-B*52:01, and HLA-DRB1*15:02 (P = 1.1 × 10 -10 , 1.5 × 10 -10 , and 1.2 × 10 -9 , respectively), which constitute a population-specific common long-range haplotype with a protective effect (P = 2.8 × 10 -10 ; OR = 0.65 [95% CI: 0.57-0.75]; haplotype frequency=0.108). Genome-wide copy-number variation (CNV) calling demonstrates rare predicted loss-of-function (pLoF) variants of the cadherin-11 gene (CDH11) conferring the risk of uRPL (P = 1.3 × 10 -4 ; OR = 3.29 [95% CI: 1.78-5.76]). Our study highlights the importance of reproductive immunology and rare variants in the uRPL etiology., (© 2024. The Author(s).)

This study evaluated the antimicrobial potency of the combination of isepamicin (ISP) for Mycobacterium abscessus species (MABS). 34 clinical MABS strains were isolated from clinical samples. Of them, 11 (32.4 %) were M. abscessus subsp. abscessus (Mab), 22 (64.7 %) were M. abscessus subsp. massiliense (Mma), and one (2.9 %) was M. abscessus subsp. bolletii (Mbo). We compared susceptibility to sitafloxacin (STFX)-ISP and clarithromycin (CLR)-ISP combinations with those of the antimicrobial agents alone, and synergistic effects were observed in 41.2 % and 17.6 % when treated with STFX-ISP and CLR-ISP. By hierarchical cluster analysis, the isolates divided into treatment-sensitive and treatment-resistant groups. Non-Mma or rough colony isolates were significantly likely to belong to the treatment-sensitive group (p = 0.024, p < 0.001, respectively). These results suggest that the ISP-containing combination could be a new therapeutic strategy for MABS, especially in cases of non-Mma: treatment-refractory subspecies, and rough morphotypes: high-virulence morphotypes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Competing Interests: The authors declare no conflict of interest.

Circulating tumor cells (CTCs) are noninvasive biomarkers that can indicate the therapeutic response and prognosis. The study aimed to investigate the cellular characteristics of CTCs focusing on monitoring during atezolizumab and bevacizumab (Atezo-Bev) therapy in patients with hepatocellular carcinoma (HCC). Peripheral blood samples were collected from 10 healthy controls and 40 patients with HCC. CTCs enriched using RosetteSep™ Human CD45 depletion cocktail were analyzed by multiparametric flow cytometry. CTC isolation was based on PanCK(+)CD45(-) cells, and CTCs exhibiting markers CD90, CD133, EpCAM, or vimentin. The total number of CTCs and the number of CTCs expressing CD90, CD133, EpCAM, and vimentin were correlated with the BCLC stage of HCC. The change in total CTC count accurately reflected the initial response to Atezo-Bev therapy. The numbers and mean fluorescence intensity of the CTC subsets expressing CD90 and EpCAM molecules decreased in patients with partial response/stable disease, and increased in patients with progressive disease and were markedly correlated with overall survival. CD90(+) and EpCAM(+) CTCs may be candidate biomarkers for the early prediction of the treatment response and the overall survival of patients with HCC receiving Atezo-Bev therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Identifying the types of exercise that enhance cerebral blood flow is crucial for developing exercise programs that enhance cognitive function. Nevertheless, few studies have explored the amount of light-intensity, short-duration exercises that individuals can easily perform on cerebral blood flow, particularly in children. We examined the effects of these exercises on the hemodynamics of the prefrontal cortex (PFC) using functional near-infrared spectroscopy. Participants comprised 41 children (aged 12.1 ± 1.5 years, 37% female) who engaged in seven light-intensity exercises, with each movement performed in two patterns lasting 10 or 20 s. Changes in oxygenated hemoglobin (oxy-Hb) levels at rest and during exercise were compared using analysis of covariance, with sex and age as covariates. Significant increases in oxy-Hb were observed in multiple regions of the PFC during all forms of exercise (including dynamic and twist stretching [66.6%, 8/12 regions, η 2  = 0.07-0.27], hand and finger movements [75.0%, 9/12 regions, η 2  = 0.07-0.16], and balance exercises (100.0%, 6/6 regions, η 2  = 0.13-0.25]), except for static stretching with monotonic movements. This study implies that short-duration, light-intensity exercises, provided that they entail a certain degree of cognitive and/or physical demands, can activate the PFC and increase blood flow., (© 2024. The Author(s).)

Aims: The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice., Methods: Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro., Results: The expression of all fibrosis-related genes was higher in Db met(-) than in WT met(-) and was suppressed by metformin. Increased levels of fibrosis-related genes, posterior capsule thickness, and collagen density were observed in the capsules of db/db mice compared with those in WT mice; these effects were suppressed by metformin. Glucose addition increased fibrosis-related gene expression in both groups of mice in vitro. When glucose was added, metformin inhibited the expression of fibrosis-related genes other than cellular communication network factor 2 ( Ccn2 ) in WT mouse cells., Conclusion: Hyperglycaemia promotes fibrosis in the mouse knee joint capsule, which is inhibited by metformin. These findings can help inform the development of novel strategies for treating knee joint capsule fibrosis., Competing Interests: None declared., (© 2024 Naito et al.)

Background: Lower gastrointestinal tract stenosis is commonly diagnosed and is typically treated with surgery or endoscopic balloon dilation (EBD). Radial incision and cutting (RIC) is a novel treatment approach that has several benefits compared with EBD and surgery. Although RIC has demonstrated a high technical success rate and has been shown to improve subjective symptoms, previous studies revealed that restenosis after RIC remain unsolved. Herein, we report the design of a prospective, multicenter, single-arm, interventional, phase II trial to evaluate the safety of local triamcinolone acetonide (TA) administration and its feasibility in preventing restenosis after RIC for lower gastrointestinal tract stenosis., Methods: The major inclusion criteria are age 20-80 years and the presence of benign stenosis in the lower gastrointestinal tract accessible by colonoscope. We will perform RIC followed by local administration of TA to 20 participants. The primary outcome is the safety of local TA administration, which will be assessed by determining the frequency of adverse events of special interest. The secondary outcomes are the technical success rate of RIC, duration of procedure, improvement in subjective symptoms, and duration of hospitalization. The outcomes, improvement in subjective symptoms, and long-term results will be evaluated using descriptive statistics, Student's t-test, and Kaplan-Meier curve, respectively., Discussion: This explorative study will provide useful information regarding the safety of TA administration after RIC, which may contribute to further investigations.

Purpose of Review: The following review will highlight the development of anamorelin to treat cancer anorexia-cachexia syndrome (CACS) including the potential benefits, limitations, and future directions., Recent Findings: Ghrelin, a 28-amino acid peptide hormone, is secreted by the stomach mucosa and regulates appetite, promotes lipogenesis, increases body weight, improves gastric motility, reduces catabolic wasting and inflammation. Several randomized, double-blind, placebo-controlled clinical trials evaluating anamorelin, a ghrelin agonist, for the treatment of CACS have reported improvement in appetite and body composition including both lean body and fat mass; however, most studies noted no improvement in physical function as assessed by measuring non-dominant hand-grip strength. Common adverse effects of anamorelin include the development of diabetes mellitus, hyperglycemia, and less frequently, hepatic abnormalities and cardiovascular events including conduction abnormalities, hypertension, and ischemic cardiomyopathy. Anamorelin has the potential to stimulate appetite, improve gastric movement, and may have anti-inflammatory effects on patients with CACS. In patients with cancer, studies involving anamorelin combined with other multimodal treatments including nutrition counseling (branched chain amino acids, omega 3 fatty acids, and other nutrients), exercise, treatment of hormonal abnormalities including hypogonadism and hypovitaminosis D, and anti-inflammatory agents are needed. Compliance with multimodality treatment has been a barrier and future studies may need to incorporate motivational counseling to promote adherence., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aims: Vedolizumab (VDZ) is a gut-selective agent with a favorable safety profile. We aimed to assess the feasibility of elective switch from other advanced therapies to VDZ and subsequent live-attenuated vaccination while continuing VDZ in patients with inflammatory bowel diseases (IBD)., Methods: We measured antibody titers specific for measles, rubella, mumps, and varicella viruses in IBD patients under immunosuppressive therapy. Those with negative titers and without vaccination history were judged unimmunized. Patients were administered vaccines while continuing VDZ or switched to VDZ if receiving other advanced therapies and then administered vaccines. Co-primary outcomes were the rate of maintaining disease severity after vaccination and the rate without vaccine-induced infection., Results: Among 107 unimmunized patients, 37 agreed to receive live-attenuated vaccines while continuing VDZ (17 patients) or after switching to VDZ (20 patients). In the 20 patients who electively switched to VDZ, disease severity was maintained except for 1 patient who developed intestinal infection. After 54 weeks, 18 patients (90%) continued to receive VDZ, excluding 2 patients who reverted to their originally administered biologics. In all 37 patients administered live-attenuated vaccines under VDZ treatment, disease severity was maintained after vaccination. Antibody titers became positive or equivocal in 34 patients (91.9%). There were no cases of vaccine-induced infection during a median observation period of 121 weeks., Conclusions: While live-attenuated vaccines are contraindicated under immunosuppressive therapy, they may be safely administered while receiving VDZ immunotherapy. Switching from other advanced therapies to VDZ and subsequently receiving live-attenuated vaccines may be a safe alternative in unimmunized patients.

Background and Aim: Inflammatory bowel disease (IBD) frequently affects younger patients and poses various challenges concerning pregnancy and childbirth. Maintaining good disease control throughout pregnancy is crucial, but expectant and pregnant patients may worry about the fetal impact of medications, leading to treatment discontinuation due to uncertainty about this issue. This study investigated the real-world drug-prescribing practices for pregnant patients with IBD in Japan and their potential connection to major congenital malformations (MCMs)., Methods: Overall, 277 female IBD patients who gave birth between 2010 and 2019 were selected from the JMDC claims database. The prescribing patterns of IBD medications and MCMs in the patients' offspring were analyzed., Results: Among pregnant IBD patients, 74.4% received at least one medication from 90 days before pregnancy to 90 days after delivery. Trends in medication prescriptions during pregnancy in 2010-2019 revealed consistent use of oral 5-ASA, variable use of topical medications, a decrease in systemic steroids, and an increase in biologics. The prevalence of MCMs in children born to IBD-affected mothers did not differ significantly between those who did and did not receive IBD medications (8.6% vs 6.8%). Although circulatory system MCMs were slightly more common in the IBD medication group (4.9% vs 1.4%), this difference was not significant. Logistic regression analysis did not reveal an association between MCM risk and first-trimester use of IBD medications, including corticosteroids and biologics., Conclusions: This study provides insights into medication patterns in pregnant IBD patients and suggests no increased risk of MCMs associated with first-trimester IBD medication use., (© 2024 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Aim: Nurses' skills and confidence in providing oral care to patients play important roles in healthcare. Studies have proved that peer-to-peer learning and assessment can help improve nurses' skills and confidence. However, no study has investigated it using an objective assessment checklist. This study investigated an oral hygiene practice training program for nursing students. It focused on their oral healthcare skills, confidence, and perspectives regarding implementing an objective structured clinical examination (OSCE)., Methods: A pre- and post-survey of 97 nursing students from a nursing school in Japan was conducted as a peer-to-peer oral health education training program that included an assessment and performance checklist., Results: Confidence in performing and assessing oral care significantly improved after attending the program. Furthermore, the changes were significantly greater in the developed program than in the training program without the checklist. The mean total assessment scores (0-25) of the first, second, third, and fourth participants in the four-student groups were 22.1, 23.4, 23.9, and 24.1, respectively. The mean scores of the second, third, and fourth participant groups were significantly higher than that of the first participant group (p < .01). Fifty-two positive and 58 negative comments were received regarding the implementation of the program with professional assessments and the checklist. The most common positive comment mentioned that the evaluation by professionals improved oral care learning and skills., Conclusions: This study developed a program to improve nursing students' confidence and oral care delivery skill building in an OSCE-style delivery., (© 2024 Japan Academy of Nursing Science.)

Background & Aims: Patients with inflammatory bowel disease (IBD) frequently develop extraintestinal manifestations (EIMs) that contribute substantially to morbidity. We assembled the largest multicohort data set to date to investigate the clinical, serologic, and genetic factors associated with EIM complications in IBD., Methods: Data were available in 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs (eg, ankylosing spondylitis [ankylosing spondylitis and sacroiliitis], primary sclerosing cholangitis [PSC], peripheral arthritis, and skin and ocular manifestations) across 4 cohorts (Cedars-Sinai Medical Center, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort). Clinical and serologic parameters were analyzed by means of univariable and multivariable regression analyses using a mixed-effects model. Within-case logistic regression was performed to assess genetic associations., Results: Most EIMs occurred more commonly in female subjects (overall EIM: P = 9.0E-05, odds ratio [OR], 1.2; 95% CI, 1.1-1.4), with CD (especially colonic disease location; P = 9.8E-09, OR, 1.7; 95% CI, 1.4-2.0), and in subjects who required surgery (both CD and UC; P = 3.6E-19, OR, 1.7; 95% CI, 1.5-1.9). Smoking increased risk of EIMs except for PSC, where there was a "protective" effect. Multiple serologic associations were observed, including with PSC (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-flagellin) and any EIM (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-Pseudomonas fluorescens-associated sequence). We identified genome-wide significant associations within major histocompatibility complex (ankylosing spondylitis and sacroiliitis, P = 1.4E-15; OR, 2.5; 95% CI, 2.0-3.1; PSC, P = 2.7E-10; OR, 2.8; 95% CI, 2.0-3.8; ocular, P = 2E-08, OR, 3.6; 95% CI, 2.3-5.6; and overall EIM, P = 8.4E-09; OR, 2.2; 95% CI, 1.7-2.9) and CPEB4 (skin, P = 2.7E-08; OR, 1.5; 95% CI, 1.3-1.8). Genetic associations implicated tumor necrosis factor, JAK-STAT, and IL6 as potential targets for EIMs. Contrary to previous reports, only 2% of our subjects had multiple EIMs and most co-occurrences were negatively correlated., Conclusions: We have identified demographic, clinical, and genetic associations with EIMs that revealed underlying mechanisms and implicated novel and existing drug targets-important steps toward a more personalized approach to IBD management., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Aim: The effects of iron on vascular calcification in rats and vascular smooth muscle cells were recently reported, but clinical studies on iron and vascular calcification are scant. We studied the associations of absolute iron deficiency, coronary artery calcification and mortality in patients with maintenance haemodialysis (MHD)., Methods: Transferrin saturation (TSAT), ferritin, mean corpuscular haemoglobin (MCH) and Agatston coronary artery calcium score (CACS) were studied at baseline in MHD patients and followed up for 3 years. Cox proportional hazard analyses for mortality and linear regression analyses for CACS were performed., Results: In 306 patients, the median age was 67 (56-81) years, dialysis duration was 76 (38-142) months, and diabetes prevalence was 42.5%. Fifty-two patients had died by 3 years. Patients with absolute iron deficiency (TSAT <20% and ferritin <100 ng/mL) (n = 102) showed significantly higher CACS (p = .0266) and C-reactive protein (p = .0011), but a lower frequency of iron formulation administration compared with patients without absolute iron deficiency at baseline (n = 204). Absolute iron deficiency was a significant predictor for 3-year cardiovascular (CV) mortality (hazard ratio: 2.08; p = .0466), but not for 3-year all-cause mortality. CACS was significant predictor for both 3-year CV and all-cause mortality (p <.05). Absolute iron deficiency and MCH were significant determinants of CACS (p < .05)., Conclusion: MHD patients with absolute iron deficiency showed significantly higher CACS than others, and absolute iron deficiency was a significant risk factor for coronary artery calcification and 3-year CV mortality in MHD patients, but was not a significant predictor for 3-year all-cause mortality., (© 2024 Asian Pacific Society of Nephrology.)

Aim: We studied the effects of overhydration (OH), Kt/Vurea and β2-microglobulin (β2-MG) on coronary artery calcification and mortality in patients undergoing haemodialysis (HD)., Methods: The Agatston coronary artery calcium score (CACS), postdialysis body composition using bioimpedance analysis, single-pool Kt/Vurea and predialysis β2-MG at baseline were assessed and followed up for 3 years in patients undergoing HD. We performed logistic regression analyses for a CACS ≥400 and Cox proportional hazard analyses for all-cause and cardiovascular mortality., Results: The study involved 338 patients with a median age of 67 (56-74) years, dialysis duration of 70 (33-141) months and diabetes prevalence of 39.1% (132/338). Patients with a CACS ≥400 (n = 222) had significantly higher age, dialysis duration, male prevalence, diabetes prevalence, C-reactive protein, predialysis β2-MG, OH, extracellular water/total body water and overhydration/extracellular water (OH/ECW) but significantly lower Kt/Vurea than patients with a CACS <400 (n = 116) (p < .05). OH/ECW, Kt/Vurea and predialysis β2-MG were significant predictors of a CACS ≥400 (p < .05) after adjusting for age, dialysis duration, serum phosphate and magnesium. In all patients, cut-off values of OH/ECW, Kt/Vurea and predialysis β2-MG for a CACS ≥400 were 16%, 1.74 and 28 mg/L, respectively. After adjusting for dialysis duration, OH/ECW ≥16%, Kt/Vurea ≥1.74 and β2-MG ≥28 mg/L were significant predictors of 3-year all-cause mortality but not 3-year cardiovascular mortality., Conclusion: Higher OH/ECW, higher predialysis β2-MG and lower Kt/Vurea values are significant risk factors for a CACS ≥400 and 3-year all-cause mortality in patients undergoing maintenance HD., (© 2024 Asian Pacific Society of Nephrology.)

Background: The AmoyDx Pan lung cancer PCR panel (AmoyDx PLC panel) has been approved as a companion diagnostic tool for multiple anticancer agents in patients with non-small cell lung cancer (NSCLC). However, the suitability of cytology specimens as samples for the AmoyDx PLC panel remains unclear. We evaluated the performance of frozen cell pellets from cytology specimens (FCPs) in the Amoy 9-in-1 assay, a preapproval assay of the AmoyDx PLC panel., Methods: We retrospectively collected data of NSCLC patients enrolled in LC-SCRUM-Asia from the Shizuoka Cancer Center between September 2019 and May 2021., Results: A total of 49 cases submitted FCPs for evaluation of oncogenic driver alterations and were assessed using Amoy 9-in-1 and next-generation sequencing (NGS) assays. The success rates of DNA and RNA analyses using the Amoy 9-in-1 were both 100%, compared with 86% and 45%, respectively, using NGS assays. Oncogenic driver alterations were detected in 27 (55%) and 23 (47%) patients using Amoy 9-in-1 and NGS, respectively. No inconsistent results were observed among 19 cases in which both assays showed successful detection. In the remaining 30 cases, 10 had inconsistent results: nine oncogenic driver alterations (3 MET, 2 ALK, 2 ROS1, and 2 KRAS) were detectable only in Amoy 9-in-1, and one epidermal growth factor receptor (EGFR) mutation was detectable only in NGS., Conclusion: FCPs can be successfully used in the AmoyDx PLC panel, with higher success rate compared with the NGS assay. The AmoyDx PLC panel may be an option in cases when insufficient tissue sample is available for the NGS assay., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Infection-induced SARS-CoV-2 seroprevalence has been studied worldwide. At Juntendo University Hospital (JUH) in Tokyo, Japan, we have consistently conducted serological studies using the blood residue of healthcare workers (HCWs) at annual health examinations since 2020. In this 2023 study ( n  = 3,594), N-specific seroprevalence (infection-induced) was examined while univariate and multivariate logistic regression analyses were performed to compute ORs of seroprevalence with respect to basic characteristics of participants. We found that the N-specific seroprevalence in 2023 was 54.1%-a jump from 17.7% in 2022, and 1.6% in 2021-with 37.9% as non-PCR-confirmed asymptomatic infection cases. Those younger than 50 (adjusted OR = 1.62; p  < .001) and recipients with 4 doses or less of vaccine had a higher risk to be N-positive, ranging from 1.45 times higher for the participants with 4 doses ( p  < .001) to 4.31 times higher for the participants with 1 dose ( p  < .001), compared to those with 5 or more doses. Our findings indicate that robust vaccination programs may have helped alleviate symptoms but consequently caused asymptomatic spread in this hospital, especially among younger HCWs. Although having four doses or less was found to be associated with higher risk of infection, the optimal constitution and intervals for effective booster vaccines warrant further investigations.

Introduction: To control the spread of severe disease caused by mutant strains of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), it is necessary to determine whether continued vaccination enhances humoral and cellular immunity., Aim: In this study, we examined the changes in humoral and cellular immunity to SARS-CoV-2 after administration of the third vaccination in Japanese adults who had received the second dose of messenger ribonucleic acid (mRNA)-1273 vaccine and the third vaccination (BNT162b2 or mRNA-1273)., Methods: We measured anti-spike antibodies in immunoglobulin G (IgG) and anti-nucleocapsid IgG titers in the serum of the vaccinated subjects. To evaluate cellular immunity, the peripheral blood mononuclear cells of inoculated individuals were cultured with spiked proteins, including those of the SARS-CoV-2 conventional strain and Omicron strain, and then subjected to enzyme-linked immunospot (ELISPOT)., Results: The results revealed that the anti-SARS-CoV-2 spike protein antibody titer increased after the third vaccination and was maintained; however, a decrease was observed at 6 months after vaccination. SARS-CoV-2 antigen-specific T helper (Th)1 and Th2 cell responses were also induced after the third vaccination and were maintained for 6 months after vaccination. Furthermore, induction of cellular immunity against Omicron strains by the omicron non-compliant vaccines, BNT162b2 or mRNA-1273, was observed., Conclusion: These findings demonstrate the effectiveness of vaccination against unknown mutant strains that may occur in the future and provide important insights into vaccination strategies., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Immune checkpoint inhibitors have promising outcomes in patients with hepatocellular carcinoma (HCC); however, there is no reliable biomarker for predicting disease progression. Circulating tumor cells (CTCs) derived from peripheral blood have attracted attention in monitoring therapeutic efficacy. In this study, CTCs were serially collected from HCC patients undergoing atezolizumab plus bevacizumab (Atezo+Bev), and changes in molecular expression and CTC numbers were analyzed to identify effective biomarkers. Changes in CTC numbers during Atezo+Bev reflected the tumor volume. Targeted RNA sequencing with next-generation sequencing (NGS) revealed that patients with elevated transforming growth factor (TGF)-β signaling molecules had a poorer response, whereas those with elevated apoptosis signaling molecules had a favorable response. In addition, compared with changes in CTC counts, changes in TGF-β signaling molecule expression in CTCs accurately and promptly predicted treatment response. Overall, NGS analysis of CTC-derived RNA showed that changes in TGF-β signaling molecules predict treatment response earlier than changes in CTC counts. These findings suggest that changes in the expression of TGF-β molecules in CTCs could serve as novel biomarkers for the early prediction of therapeutic response in patients with unresectable HCC undergoing Atezo+Bev.

Background: It is crucial to pinpoint the metabolites that cause Crohn's disease (CD) and ulcerative colitis (UC) to comprehend their pathogenesis and identify possible targets for therapy. To achieve this goal, we performed the first metabolome-wide Mendelian randomization (MR) study of Japanese patients with CD and UC., Methods: As exposure datasets, genetic instruments with blood-circulating metabolites were obtained from the Tohoku Medical Megabank Organization, which includes 204 metabolites from the genome-wide association study data of 7843 Japanese individuals. As outcome datasets, we enrolled Japanese patients with CD (n = 1803), Japanese patients with UC (n = 1992), and healthy controls (n = 2022). The main analysis utilized the inverse variance-weighted method, while stability of the findings was evaluated through sensitivity analyses., Results: After single nucleotide polymorphism (SNP) filtering, 169 SNPs for 45 metabolites were available for MR. Genetically predicted elevated circulating trans-glutaconic acid and tryptophan were associated with a lower CD risk (odds ratio [OR], 0.68; P = 5.95 × 10-3; and OR, 0.64; P = 1.90 × 10-2, respectively). Genetically predicted elevated caffeic acid was associated with a lower UC risk (OR, 0.67; P = 4.2 × 10-4), which remained significant after multiple testing correction. We identified a causal link between UC and 3-hydroxybutyrate (OR, 2.21; P = 1.41 × 10-2), trans-glutaconic acid (OR, 0.72; P = 1.77 × 10-2), and 2-hydroxyvaleric acid (OR, 1.31; P = 4.23 × 10-2). There was no evidence of pleiotropy or reverse causal effects for these candidate metabolites., Conclusions: In our metabolome-wide MR study, we discovered a notable protective effect of caffeic acid against UC., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Although durvalumab plus tremelimumab (Dur/Tre) has been approved as first-line therapy for patients with unresectable hepatocellular carcinoma (u-HCC), its outcomes in real-world clinical practice are unclear. The present study aimed to evaluate the efficacy and safety of Dur/Tre treatment. This multicenter study was conducted between March 2023 and January 2024, and included 120 patients with u-HCC treated with Dur/Tre. Among the patients, 44 had no history of systemic treatment. Progression-free survival (PFS), therapeutic response and adverse events (AEs) were assessed. The objective response rate (ORR) and disease control rates (DCR) were 15.8 and 53.3%, respectively. The median PFS was 3.9 months. The incidence rates of AEs of any grade and those grade 3 or higher were 83.3 and 36.7%, respectively. Liver injury was the most frequent AE of any grade and grade 3 or higher. Although there was no significant difference in ORR and PFS between the first and later line groups (ORR 15.8 vs. 15.7%, P=0.986; PFS 4.5 vs. 3.6 months, P=0.213), there was a significant difference in DCR between the two groups (65.8 vs. 45.9%, P=0.034). No significant differences were noted between the first- and later-line treatment groups regarding the incidence rate of AEs. Decision tree analysis revealed that poor liver function and advanced age were significant variables for discontinuation owing to AEs. In conclusion, Dur/Tre as first-line therapy had better disease control responses compared with later-line therapy; however, this regimen should be carefully administered to patients with deteriorating hepatic function or advanced age., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Shimose et al.)

Background/aims: During endoscopy, white spots (WS) are sometimes observed around benign or malignant colorectal tumors; however, few reports have investigated WS, and their significance remains unknown. Therefore, we investigated the significance of WS from clinical and pathological viewpoints and evaluated its usefulness in endoscopic diagnosis., Methods: Clinical data of patients with lesions diagnosed as epithelial tumors from January 1, 2019, to December 31, 2020, were analyzed (n=3,869). We also performed a clinicopathological analysis of adenomas or carcinomas treated with endoscopic resection (n=759). Subsequently, detailed pathological observations of the WS were performed., Results: The positivity rates for WS were 9.3% (3,869 lesions including advanced cancer and non-adenoma/carcinoma) and 25% (759 lesions limited to adenoma and early carcinoma). Analysis of 759 lesions showed that the WS-positive lesion group had a higher proportion of cancer cases and larger tumor diameters than the WS-negative group. Multiple logistic analysis revealed the following three statistically significant risk factors for carcinogenesis: positive WS, flat lesions, and tumor diameter ≥5 mm. Pathological analysis revealed that WS were macrophages that phagocytosed fat and mucus and were white primarily because of fat., Conclusions: WS are cancer-related findings and can become a new criterion for endoscopic resection in the future.

Background and Aim: The number of older patients with ulcerative colitis is increasing; however, limited data exist regarding the differences between elderly- and non-elderly-onset ulcerative colitis. We aimed to compare the clinical practice and course of elderly-onset ulcerative colitis with those of non-elderly-onset ulcerative colitis., Methods: We selected older patients with ulcerative colitis and divided them into the elderly- and non-elderly-onset ulcerative colitis groups according to their age at onset. We compared the cumulative systemic steroid-free, molecular targeting drug-free, and surgery-free rates between the two groups. We performed a multivariate analysis to identify the clinical factors related to systemic steroid administration, the use of molecular targeting drugs, surgery, and death., Results: We collected data of 2669 and 277 elderly and non-elderly-onset ulcerative colitis patients, respectively. The cumulative systemic steroid-free rate of elderly-onset ulcerative colitis was significantly lower than that of non-elderly-onset ulcerative colitis. However, no difference was observed in the cumulative molecular targeting drugs and surgery-free rates between the two groups. Elderly-onset ulcerative colitis significantly increased the risk of systemic steroid administration and death but not the use of molecular targeting drugs and surgery., Conclusion: The disease severity of ulcerative colitis and clinical practice may not differ between the elderly- and non-elderly-onset groups. However, elderly-onset ulcerative colitis was associated with increased mortality risk. Thus, we need to pay attention to the patients' condition and appropriate timing of surgery for patients with elderly-onset ulcerative colitis., (© 2024 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Purpose: This study aimed to investigate the usefulness of a newly developed oral simulator for nursing students' oral assessment education on oral diseases and symptoms., Materials and Methods: The participants were first-year students (n=105) at a nursing school in Japan. Ten identical oral simulators with angular cheilitis, missing teeth, dental caries, calculus, periodontitis, hypoglossal induration, food debris, and crust formation were created by a team of dentists. After a 45-minute lecture programme for oral assessment performance with the Oral Health Assessment Tool (OHAT), the ability test with the simulators and the OHAT as well as test feedback were conducted in a 30-minute practical programme. To evaluate the effectiveness of the programmes, questionnaires and ability tests with slides of oral images were conducted at baseline and after the programme., Results: Ninety-nine students (94.3%) participated in this study. The results of the ability test with the simulators and the OHAT in the practical programme showed that the correct answer rates of assessing tongue, gingiva, present teeth, and oral pain were less than 40%. Their levels of confidence, perception, and oral assessment performance were statistically significantly higher after the programmes than they were at baseline. Their level of confidence in assessing the need for dental referral had the largest increase in scores compared to the lowest scores at baseline in the nine post-programme assessment categories., Conclusions: This study identified several problems with nursing students' oral assessment skills and improvements of their oral assessment confidence, perceptions and performance.

In patients presenting neck pain and hemiparesis, differentiation between cerebral infarction and cervical spinal epidural hematoma is vital yet challenging, particularly when magnetic resonance imaging (MRI) is not feasible. A 59-year-old woman presented with a sudden onset of left-sided hemiparesis and neck pain. MRI was contraindicated because the patient underwent embolization in childhood. Head computed tomography (CT) revealed no evidence of hemorrhage or early ischemic signs. Cervical CT revealed no evidence of hematoma within the spinal canal. Myelography and CT myelography revealed no significant cervical spine abnormalities. The diagnosis was cerebral infarction. Cervical spine MRI is the gold standard examination for diagnosing cervical spinal epidural hematoma, but cervical spine CT, myelography, and CT myelography may be useful when MRI is contraindicated., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tanaka et al.)