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Risa Hirata,1 Naoko E Katsuki,1 Hitomi Shimada,2 Eiji Nakatani,3 Kiyoshi Shikino,4,5 Chihiro Saito,6 Kaori Amari,7 Yoshimasa Oda,8 Midori Tokushima,1 Masaki Tago1 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Shimada Hospital of Medical Corporation Chouseikai, Saga, Japan; 3Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan; 4Department of General Medicine, Chiba University Hospital, Chiba, Japan; 5Department of Community-Oriented Medical Education, Chiba University Graduate School of Medicine, Chiba, Japan; 6Shizuoka General Hospital, Shizuoka, Japan; 7Department of Emergency Medicine, Saga-Ken Medical Centre Koseikan, Saga, Japan; 8Department of General Medicine, Yuai-Kai Foundation and Oda Hospital, Saga, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jpPurpose: There has been no large-scale investigation into the association between the use of lemborexant, suvorexant, and ramelteon and falls in a large population. This study, serving as a pilot investigation, was aimed at examining the relationship between inpatient falls and various prescribed hypnotic medications at admission.Patients and Methods: This study was a sub-analysis of a multicenter retrospective observational study conducted over a period of 3 years. The target population comprised patients aged 20 years or above admitted to eight hospitals, including chronic care, acute care, and tertiary hospitals. We extracted data on the types of hypnotic medications prescribed at admission, including lemborexant, suvorexant, ramelteon, benzodiazepines, Z-drugs, and other hypnotics; the occurrence of inpatient falls during the hospital stay; and patients’ background information. To determine the outcome of inpatient falls, items with low collinearity were selected and included as covariates in a forced-entry binary logistic regression analysis.Results: Overall, 150,278 patients were included in the analysis, among whom 3,458 experienced falls. The median age of the entire cohort was 70 years, with men constituting 53.1%. Binary logistic regression analysis revealed that the prescription of lemborexant, suvorexant, and ramelteon at admission was not significantly associated with inpatient falls.Conclusion: The administration of lemborexant, suvorexant, and ramelteon at admission may not be associated with inpatient falls.Keywords: lemborexant, hypnotics, in-hospital falls, risk factor

Masaki Tago,1 Risa Hirata,1 Naoko E Katsuki,1 Eiji Nakatani,2 Midori Tokushima,1 Tomoyo Nishi,1 Hitomi Shimada,3 Shizuka Yaita,1 Chihiro Saito,4 Kaori Amari,5 Kazuya Kurogi,6 Yoshimasa Oda,7 Kiyoshi Shikino,8,9 Maiko Ono,10 Mariko Yoshimura,11 Shun Yamashita,1 Yoshinori Tokushima,1 Hidetoshi Aihara,1 Motoshi Fujiwara,1 Shu-ichi Yamashita1 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan; 3Shimada Hospital of Medical Corporation Chouseikai, Saga, Japan; 4Shizuoka General Hospital, Shizuoka, Japan; 5Department of Emergency Medicine, Saga-Ken Medical Centre Koseikan, Saga, Japan; 6Department of General Medicine, National Hospital Organization Ureshino Medical Center, Saga, Japan; 7Department of General Medicine, Yuai-Kai Foundation and Oda Hospital, Saga, Japan; 8Department of General Medicine, Chiba University Hospital, Chiba, Japan; 9Department of Community-Oriented Medical Education, Chiba University Graduate School of Medicine, Chiba, Japan; 10Department of General Medicine, Karatsu Municipal Hospital, Saga, Japan; 11Safety Management Section, Saga University Hospital, Saga, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jpPurpose: We conducted a pilot study in an acute care hospital and developed the Saga Fall Risk Model 2 (SFRM2), a fall prediction model comprising eight items: Bedriddenness rank, age, sex, emergency admission, admission to the neurosurgery department, history of falls, independence of eating, and use of hypnotics. The external validation results from the two hospitals showed that the area under the curve (AUC) of SFRM2 may be lower in other facilities. This study aimed to validate the accuracy of SFRM2 using data from eight hospitals, including chronic care hospitals, and adjust the coefficients to improve the accuracy of SFRM2 and validate it.Patients and Methods: This study included all patients aged ≥ 20 years admitted to eight hospitals, including chronic care, acute care, and tertiary hospitals, from April 1, 2018, to March 31, 2021. In-hospital falls were used as the outcome, and the AUC and shrinkage coefficient of SFRM2 were calculated. Additionally, SFRM2.1, which was modified from the coefficients of SFRM2 using logistic regression with the eight items comprising SFRM2, was developed using two-thirds of the data randomly selected from the entire population, and its accuracy was validated using the remaining one-third portion of the data.Results: Of the 124,521 inpatients analyzed, 2,986 (2.4%) experienced falls during hospitalization. The median age of all inpatients was 71 years, and 53.2% were men. The AUC of SFRM2 was 0.687 (95% confidence interval [CI]:0.678– 0.697), and the shrinkage coefficient was 0.996. SFRM2.1 was created using 81,790 patients, and its accuracy was validated using the remaining 42,731 patients. The AUC of SFRM2.1 was 0.745 (95% CI: 0.731– 0.758).Conclusion: SFRM2 showed good accuracy in predicting falls even on validating in diverse populations with significantly different backgrounds. Furthermore, the accuracy can be improved by adjusting the coefficients while keeping the model’s parameters fixed.Keywords: accidental falls, inpatients, validation study, accident prevention

Cases of slowness among patients who spent large amounts of time to perform daily activities were first reported in 1974, and described as primary obsessional slowness (POS). It was observed that it was neither obsessive thoughts nor compulsions that directly hindered their daily activities. However, in more than 20 years following the original report, the diagnostic independence of POS remains controversial, some insisting that obsessional slowness can be explained as secondary. The authors experienced four cases in Japan which share the same characteristics as the original cases. Long-term observation and treatment has led us to support the diagnostic independence of POS. Slowness remained after other accompanying symptoms of obsessive-compulsive disorder had been successfully treated, showing that the slowness of our patients was not secondary.

Abstract: Background: Reducing near‐fatal asthma exacerbations is a critical problem in asthma management. Objectives: To determine patterns of factors preceding asthma exacerbations in a real‐world setting. Methods: In a nationwide prospective study of 190 patients who had experienced near‐fatal asthma exacerbation, cluster analysis was performed using asthma symptoms over the 2‐week period before admission. Results: Three distinct clusters of symptoms were defined employing the self‐reporting of a visual analogue scale. Cluster A (42.1%): rapid worsening within 7.4 hours from moderate attack to admission, young to middle‐aged patients with low Body mass index and tendency to depression who had stopped anti‐asthma medications, smoked, and hypersensitive to environmental triggers and furred pets. Cluster B (40.0%): fairly rapid worsening within 48 hours, mostly middle‐aged and older, relatively good inhaled corticosteroid (ICS) or ICS/long‐acting beta‐agonist (LABA) compliance, and low perception of dyspnea. Cluster C (17.9%): slow worsening over 10 days before admission, high perception of dyspnea, smokers, and chronic daily mild‐moderate symptoms. There were no differences in overuse of short‐acting beta‐agonists, baseline asthma severity, or outcomes after admission for patients in these 3 clusters. Conclusion: To reduce severe or life‐threatening asthma exacerbation, personalized asthma management plans should be considered for each cluster. Improvement of ICS and ICS/LABA compliance and cessation of smoking are important in cluster A. To compensate for low perception of dyspnea, asthma monitoring of peak expiratory flow rate and/or exhaled nitric oxide would be useful for patients in cluster B. Avoidance of environmental triggers, increase usual therapy, or new anti‐type 2 response‐targeted therapies should be considered for cluster C. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop new risk classifications for conversion to Alzheimer's disease (AD) by comparing the relative reliability of classifiers in patients with mild cognitive impairment (MCI). The 397 MCI subjects and all baseline data, including characteristics, neuropsychological tests, cerebrospinal fluid biomarkers and MRI findings in Alzheimer's Disease Neuroimaging Initiative (ADNI), were used for analysis by Cox proportional hazard regression, bootstrap sampling, and c-index. Multivariate Cox regression analysis revealed the following factors to be associated with increased risk of conversion from MCI to AD during the 53-month follow-up period: AVLT 30-minute delayed recall, AVLT trial 1, Boston naming, logical delayed recall, trail-making B, CDR-sob, ADAS13, the cortical thickness of the right inferior temporal lobe (st91ta), and the left hippocampus volume. The combinations of ADAS13 at a cutoff point of 15.67 with CDR-sob at 1.5 or with the cortical thickness of the right inferior temporal lobe at 2.56 mm3 produced high conversion rates of 92.7% (82.4%-100.0%) and 88.8% (77.3%-100.0%), respectively, at 48 months. The discriminative ability based on c-index for the proposed combination was 0.68. The sample size was estimated as 504 in the group with a combination of ADAS13 and CDR-sob whose conversion rate is highest. The combination of ADAS13 with CDR-sob at an optimal cutoff point has a high reliability in classifying the MCI patients into high- and low-risk conversion to AD and will be benefit for patients' assessment and potentially facilitate the clinical development of novel therapeutics. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the impact of renal function impairment on long-term survival outcomes and adjuvant therapy in patients with pancreatic cancer undergoing pancreaticoduodenectomy (PD)., Methods: In this study, 264 patients who underwent PD for pancreatic head cancer between 2011 and 2021 were retrospectively analyzed. The patients were subsequently categorized into three groups according to the estimated glomerular filtration rate: normal group (> 90 mL/min/1.73 m 2 , n = 73), moderate group (45-90 mL/min/1.73 m 2 , n = 176), and severe group (< 45 mL/min/1.73 m 2 , n = 15). The primary outcomes evaluated were postoperative complications, overall survival (OS), and relapse-free survival (RFS). Additionally, the completion of adjuvant therapy and risk factors for adjuvant therapy discontinuation were analyzed., Results: The total proportion of patients with complications was significantly higher in the severe group (p = 0.008). The proportion of patients with severe complications (Clavien-Dindo classification ≥ IIIa) did not significantly differ between the chronic kidney disease (CKD) groups (p = 0.730). The proportion of patients in whom adjuvant therapy was completed was notably lower in the severe group (p = 0.011). Multiple logistic regression analysis revealed that CKD groups and hemoglobin levels ≤ 11.5 g/dL were independent predictors of adjuvant therapy completion failure (p = 0.016 and p = 0.016). There was no significant difference in the OS and RFS rates between the CKD groups (p = 0.499, p = 0.688)., Conclusions: In patients with pancreatic cancer and CKD, performing PD safely may be feasible; however, adjuvant therapy completion is challenging., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Expiratory flow is an important factor in the achievement of airway clearance that is required to prevent postoperative pneumonia (POP). Although peak expiratory flow (PEF) has been shown to predict the occurrence of POP in lung cancer patients after lobectomy, its predictive power in relation to esophagectomy for esophageal cancer remains unknown. This study assesses PEF as a predictor of POP in patients with esophageal cancer undergoing radical esophagectomy. We conducted a single-center, retrospective cohort study of patients who underwent radical esophagectomy with gastric tube reconstruction at our institution between January 2007 and December 2022. Preoperative pulmonary functions, including PEF, were assessed before surgery. Additionally, POP was diagnosed as a Clavien-Dindo classification of Grade II or higher. Survival and pneumonia incidence were compared using the Kaplan-Meier method. Logistic regression analysis was used to examine the relationship between these variables and POP. The study included 513 patients, of which 441 were men. POP occurred in 86 patients (16.7%). When all patients were stratified by %PEF into two groups, the group with %PEF lower that 80% had significantly poorer prognosis and higher incidence of pneumonia. Multivariable logistic regression analysis indicated that %PEF (OR: 0.986, 95%CI: 0.974-0.999, P = 0.030), along with age, BMI, preoperative treatment, and recurrent laryngeal nerve palsy were independent protective factors against POP. These results reveal that %PEF predicts the development of POP following esophagectomy for esophageal cancer., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Prior research has indicated a correlation between the birth season and life expectancy; however, many of these studies did not sufficiently account for comorbidities. In this comprehensive investigation, we aimed to meticulously explore the association between the birth month and life expectancy, giving due consideration to comorbidities. We used a robust dataset derived from Taiwan's National Health Insurance Research Database (2000-2013), which allowed us to conduct a thorough examination. We divided our participants into four groups based on their season of birth: spring, summer, autumn, and winter. Propensity score matching was used to ensure an equitable distribution of demographic and clinical characteristics across the groups. Propensity scores were computed using logistic regression. Our model incorporated a broad range of demographic factors and comorbidities, providing rigorous adjustment for potential confounders. Our findings revealed a significantly increased risk of all-cause mortality among individuals born in spring, even after stringent adjustment for demographic factors and comorbidities. People born in spring demonstrated a 1.05-fold increase in the risk of all-cause mortality, with a hazard ratio of 1.05 and a 95% confidence interval of 1.01-1.09. Our study provides compelling evidence that helps understand the potential long-term impacts of a person's birth season, which acts as a proxy for pregnancy / early-life environmental exposure, on life expectancy. These findings underscore the crucial need for additional research to illuminate the underlying biological and environmental mechanisms linking the birth season and lifespan of a person. The elucidation of these links could guide the development of innovative health promotion and disease prevention strategies that are tailored to an individual's birth season., (© 2024. The Author(s).)

Objective: Vitamin D deficiency (VDD) is common among young women and causes various health problems, including those that occur during pregnancy and childbirth. Thus, we investigated the risk factors for VDD in young Japanese women and developed a simple risk scoring system called Vitamin D Deficiency Predicting Scoring (ViDDPreS)., Design: A cross-sectional study, using the following factors for multivariate logistic regression analysis to create the ViDDPreS score: residential area, season, cumulative ambient ultraviolet-B irradiation, BMI, vitamin D supplement use, sun exposure habits, frequency of habitual food intake and eating habits. The subjects were randomly divided into development and test sets for analysis. Serum 25-hydroxivitamin D concentration of less than 20 ng/ml was defined as VDD., Setting: Four regions (Hokkaido/Tohoku, Kanto, Chubu/Kinki/Shikoku and Kyushu/Okinawa) in Japan., Participants: Five hundred and eighty-three healthy women aged 18-40 years., Results: In the development set, the VDD group (68·4 %) had higher proportions of the following variables than the non-VDD group: residential area outside the Kanto region; blood samples obtained in winter; low BMI (<18·5 kg/m 2 ); vitamin D supplement non-users; short time regularly spent outside on weekdays; intake of fish, vitamin D-abundant fish, dried fish and redfish less than once a week. VDD risk was classified as low, medium or high according to the ViDDPreS scores including these contributing factors, with a test set C-index of 0·671., Conclusion: We identified the risk factors for VDD in young Japanese women and developed a simple risk scoring system that enables us to assess VDD risk and aid in the development of appropriate prevention and treatment strategies for this population.

Competing Interests: Conflicts of interest Author Ubukata is an employee of Sato Pharmaceutical Co, Ltd.

Background: Western guidelines often recommend biguanides as the first-line treatment for diabetes. However, dipeptidyl peptidase-4 (DPP-4) inhibitors, alongside biguanides, are increasingly used as the first-line therapy for type 2 diabetes (T2DM) in Japan. However, there have been few studies comparing the effectiveness of biguanides and DPP-4 inhibitors with respect to diabetes-related complications and cardio-cerebrovascular events over the long term, as well as the costs associated., Objective: We aimed to compare the outcomes of patients with T2DM who initiate treatment with a biguanide versus a DPP-4 inhibitor and the long-term costs associated., Methods: We performed a cohort study between 2012 and 2021 using a new-user design and the Shizuoka Kokuho database. Patients were included if they were diagnosed with T2DM. The primary outcome was the incidence of cardio-cerebrovascular events or mortality from the initial month of treatment; and the secondary outcomes were the incidences of related complications (nephropathy, renal failure, retinopathy, and peripheral neuropathy) and the daily cost of the drugs used. Individuals who had experienced prior events during the preceding year were excluded, and events within 6 months of the start of the study period were censored. Propensity score matching was performed to compare between two groups., Results: The matched 1:5 cohort comprised 529 and 2,116 patients who were initially treated with a biguanide or a DPP-4 inhibitor, respectively. Although there were no significant differences in the incidence of cardio-cerebrovascular events or mortality and T2DM-related complications between the two groups (p = 0.139 and p = 0.595), daily biguanide administration was significantly cheaper (mean daily cost for biguanides, 61.1 JPY; for DPP-4 inhibitors, 122.7 JPY; p<0.001)., Conclusion: In patients with T2DM who initiate pharmacotherapy, there were no differences in the long-term incidences of cardio-cerebrovascular events or complications associated with biguanide or DPP-4 use, but the former was less costly., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nakatani 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.)

Background: The increasing prevalence of frailty has gained considerable attention due to its profound influence on clinical outcomes. However, our understanding of the progression of frailty and long-term clinical outcomes in older individuals with atrial fibrillation remains scarce., Methods: Using data from 2012 to 2018 from a comprehensive claims database incorporating primary and hospital care records in Shizuoka, Japan, we selected patients aged ≥65 years with atrial fibrillation who initiated oral anticoagulant therapy. The trajectory of frailty was plotted using Sankey plots, illustrating the annual changes in their frailty according to the electronic frailty index during a 3-year follow-up after oral anticoagulant initiation, along with the incidence of clinical adverse outcomes. For deceased patients, we assessed their frailty status in the year preceding their death., Results: Of 6247 eligible patients (45.1% women; mean age, 79.3±8.0 years) at oral anticoagulant initiation, 7.7% were categorized as fit (electronic frailty index, 0-0.12), 30.1% as mildly frail (>0.12-0.24), 35.4% as moderately frail (>0.24-0.36), and 25.9% as severely frail (>0.36). Over the 3-year follow-up, 10.4% of initially fit patients transitioned to moderately frail or severely frail. Conversely, 12.5% of severely frail patients improved to fit or mildly frail. Death, stroke, and major bleeding occurred in 23.4%, 4.1%, and 2.2% of patients, respectively. Among the mortality cases, 74.8% (N=1183) and 3.5% (N=55) had experienced moderately or severely frail and either a stroke or major bleeding in the year preceding their death, respectively., Conclusions: In a contemporary era of atrial fibrillation management, a minor fraction of older patients on oral anticoagulants died following a stroke or major bleeding. However, their frailty demonstrated a dynamic trajectory, and a substantial proportion of death was observed after transitioning to a moderately or severely frail state., Competing Interests: Dr Kohsaka received an investigator-initiated grant from Novartis. Dr Kumamaru received consultation fees from Mitsubishi Tanabe Pharma and speaker’s fees from Pfizer Japan, Inc, and Johnson & Johnson K.K. Dr Yamamoto received consultation fees from Mitsubishi Tanabe Pharma, speaker’s fees from Chugai Pharmaceutical Co., Ltd., and Ono Pharmaceutical Co., Ltd., and payment for an article from Astellas Pharma, Inc. Dr Miyata received a research grant from AstraZeneca K.K. for an independent research project through the PeoPLe Consortium at Keio University. Drs Nakamaru, Nishimura, Kumamaru, Yamamoto, Miyata, and Kohsaka are affiliated with the Department of Healthcare Quality Assessment, The University of Tokyo. This department is a social collaboration department supported by the National Clinical Database, Johnson & Johnson K.K., Nipro Corporation, and Intuitive Surgical Sàrl. The other authors report no conflicts.

Background and Objective: Pooled analyses of previous randomized controlled trials reported that antifibrotics improved survival in patients with idiopathic pulmonary fibrosis (IPF), but the results were only based on short-term outcome data from selected patients who met strict criteria. Observational studies/meta-analyses also suggested that antifibrotics improve survival, but these studies failed to control for immortal time bias that considerably exaggerates drug effects. Therefore, whether antifibrotics truly improve long-term survival in patients with IPF in the real world remains undetermined and requires external validity., Methods: We used data from the Japanese National Claims Database to estimate the intention-to-treat effect of antifibrotics on mortality. To address immortal time bias, we employed models treating antifibrotic initiation as a time-dependent covariate and target trial emulation (TTE), both incorporating new-user designs for antifibrotics and treating lung transplantation as a competing event., Results: Of 30,154 patients with IPF, 14,525 received antifibrotics. Multivariate Fine-Gray models with antifibrotic initiation as a time-dependent covariate revealed that compared with no treatment, nintedanib (adjusted hazard ratio [aHR], 0.85; 95% confidence interval [CI], 0.81-0.89) and pirfenidone (aHR, 0.89; 95% CI, 0.86-0.93) were associated with reduced mortality. The TTE model also replicated the associations of nintedanib (aHR, 0.69; 95% CI, 0.65-0.74) and pirfenidone (aHR, 0.81; 95% CI, 0.78-0.85) with reduced mortality. Subgroup analyses confirmed this association regardless of age, sex, and comorbidities, excluding certain subpopulations., Conclusions: The results of this large-scale real-world analysis support the generalizability of the association between antifibrotics and improved survival in various IPF populations., (© 2024. The Author(s).)

Introduction: The cognitive function score (CFS) is a public scale for assessing the activities of daily living (ADL) in older adults with dementia in Japan. In contrast, the scores of the revised Hasegawa's dementia scale (HDS-R), an easy-to-use dementia screening tool developed in Japan, are significantly correlated with mini-mental state examination scores and are widely utilized in various countries. This novel study aimed to elucidate the previously unexplored criterion-related validity of the CFS and HDS-R and the Bedriddenness Rank (BR), Barthel index (BI), and Katz index (KI)., Methods: This was a multicenter retrospective study and a secondary analysis of our previous study. The study included patients aged ≥20 years hospitalized in chronic care settings between April 1, 2018, and March 31, 2021. We collected data from medical charts on admission, including age, sex, the BR, CFS, BI, KI, and HDS-R scores. Correlations between the CFS and HDS-R score, as well as between the BR and BI or KI, were analyzed using Spearman's rank correlation coefficients., Results: A total of 749 participants were included in the analysis of criterion-related validity between the CFS and HDS-R. In the CFS cohort analysis, 202 patients (27.0%) were categorized as having a normal CFS, and the median HDS-R score was 18 (range: 6-26). The correlation coefficient between the CFS and HDS-R scores was -0.834 ( p < 0.001). The correlation coefficient between BR and BI was -0.741 ( p < 0.001), BR and KI was -0.740 ( p < 0.001)., Conclusion: The CFS revealed significant criterion-related validity compared with the established cognitive assessment scale, the HDS-R. The BR also demonstrated significant criterion-related validity with the BI and KI., Competing Interests: Masaki Tago is supported by grants from the Japan Society for the Promotion of Science, JSPS KAKENHI (Grant No. JP21H03166)., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Pancreatic cancer presents a critical health issue characterized by low survival rates. Identifying risk factors in specific populations, such as those with diabetes, is crucial for early detection and improved outcomes. This study aimed to identify risk factors for pancreatic cancer in diabetic patients using a longitudinal cohort from the Shizuoka Kokuho database, spanning April 2012 to September 2021. Diabetic patients were identified and monitored for the onset of pancreatic cancer. Factors analyzed included age, sex, the Elixhauser comorbidity index, and specific comorbidities. Statistical analyses involved univariate and multivariate Cox proportional hazards regression. The study identified 212,775 as diabetic patients and 1755 developed pancreatic cancer during the period. The annual incidence rate of pancreatic cancer in this group was 166.7 cases per 100,000 person-years. The study identified older age, male sex, a history of liver disease, chronic pancreatitis, and pancreatic cystic lesions as significant risk factors for pancreatic cancer in diabetic patients. The study also highlighted the absence of a significant association between diabetes type or diabetic complications and the onset of pancreatic cancer. These findings may aid in the early diagnosis of pancreatic cancer in diabetic patients and may inform revisions in screening practices in diabetic patients., (© 2024. The Author(s).)

Background: After radical resection for esophageal cancer, death within 1 year of surgery can occur due both to recurrence and to other diseases, even after postoperative complications have been overcome. This study identified risk factors for early death within 1 year of esophagectomy for reasons other than death in hospital in patients undergoing esophagectomy for esophageal cancer or esophagogastric junction cancer., Methods: We reviewed 366 patients who underwent esophagectomy without adjuvant treatment between January 2009 and July 2022 for thoracic esophageal cancer or esophagogastric junction cancer. Patients who died within 1 year excluding in-hospital death were compared with those who did not. Multivariable logistic regression analysis was used to identify predictors of death within 1 year after surgery., Results: Death within 1 year occurred in 32 of 366 patients, 24 from primary disease and 8 from other diseases. Deaths within 1 year were significantly older than the other cases, had significantly lower % vital capacity (%VC), and occurred significantly more often in cases in advanced stages of disease. In a multivariable analysis, a systemic inflammation score (SIS) based on serum albumin level and lymphocyte-to-monocyte ratio was identified as an independent predictor of death within 1 year. As SIS increased, %VC decreased significantly, and CRP level and neutrophil-lymphocyte ratio increased significantly. There was no relationship between SIS and pN. Death within 1 year increased as SIS increased (p = 0.001 for trend)., Conclusion: SIS assessment undertaken before beginning esophageal cancer treatment is a useful predictor of death within 1 year of surgery., (© 2024. The Author(s), under exclusive licence to The Author(s) under exclusive licence to The Japan Esophageal Society.)

Lactononadecapeptide (LNDP; NIPPLTQTPVVVPPFLQPE), a casein-derived peptide comprising 19 residues, is known for its capacity to enhance cognitive function. This study aimed to explore the transepithelial transport and stability of LNDP. Results showed that LNDP retained over 90% stability after 2 h of treatment with gastrointestinal enzymes. The stability of LNDP on Caco-2 cell monolayers ranged from 93.4% ± 0.9% to 101.1% ± 1.2% over a period of 15-60 min, with no significant differences at each time point. The permeability of LNDP across an artificial lipid membrane was very low with the effective permeability of 3.6 × 10 -11 cm/s. The Caco-2 assay demonstrated that LNDP could traverse the intestinal epithelium, with an apparent permeability of 1.22 × 10 -6 cm/s. Its transport was significantly inhibited to 67.9% ± 5.0% of the control by Gly-Pro, a competitor of peptide transporter 1 (PEPT1). Furthermore, PEPT1 knockdown using siRNA significantly inhibited LNDP transport by 77.6% ± 1.9% in Caco-2 cell monolayers. The LNDP uptake in PEPT1-expressing HEK293 cells was significantly higher (54.5% ± 14.6%) than that in mock cells. These findings suggest that PEPT1 plays a crucial role in LNDP transport, and LNDP exhibits good resistance to gastrointestinal enzymes.