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Objective: There is no established consensus or guidelines for wound management after revascularization for patients with chronic limb-threatening ischemia (CLTI) without severe infection. This study is designed to evaluate the clinical effect of the wound management strategy on toe wounds after revascularization for CLTI., Methods: This retrospective cohort study was performed at eight institutions affiliated with Keio University School of Medicine in Japan and included 261 patients who underwent revascularization for CLTI between April 2019 and July 2021. We identified 132 patients with toe wounds from the database who had restored in-line blood flow to the foot. Patients were divided into two groups by the timing of toe resection after revascularization, which dictated the wound management policy. Group A (62 patients) underwent early toe amputation for suspected osteomyelitis, whereas group B (70 patients) underwent watchful waiting. The primary outcome was wound healing after revascularization; the secondary outcome was major amputation. We compared outcomes between groups A and B after propensity score matching., Results: Using propensity score matching, each patient in group A (33 patients) was matched with a patient in group B (33 patients). Wound healing in matched group A was significantly better than that in matched group B (respectively: 1-year wound healing rate: 90.0% vs 68.2%, P < .001; median wound healing time: 65 days vs 258 days, P < .01). Although five major amputations were necessary in matched group B, none were required in matched group A (P = .05). The high rate of major amputations in group B was attributed to the sudden exacerbation of infection. Limb salvage rate in matched group A exceeded matched group B (100.0% vs 90.5%: 1-year limb salvage rate, P = .02)., Conclusions: Early toe amputation for highly suspected osteomyelitis in patients with CLTI with toe wounds may expedite wound healing compared with watchful waiting, potentially avoiding unnecessary major amputation. Considering the wound management strategy is crucial when evaluating wound healing outcomes in patients with CLTI with revascularization., Competing Interests: Disclosures N.F. has served as a consultant for Japan Lifeline and Cook Medical. S.O. served as a consultant for Medico’s Hirata. H.O. received educational grant from Cardinal Health, Japan Blood Products Organization, JMS, Taiho Pharmaceutical, Teijin Pharma Limited, MSD, Kaken Pharmaceutical, Sanofi, Dainippon Sumitomo Pharma, Mitsubishi Tanabe Pharma Corporation, Nihon Pharmaceutical, Japan Lifeline, Limfix, Medtronic Japan, Otsuka Pharmaceutical Factory, Daiichi Sankyo Company, Johnson & Johnson, Otsuka Pharmaceutical, Kowa, and W. L. Gore & Associates. Y.K. received lecture fees from Chugai Pharmaceutical, Taiho Pharmaceutical, Asahi Kasei Pharma Corporation, Otsuka Pharmaceutical Factory, Ono Pharmaceutical, Shionogi, AstraZeneca, Ethicon, Bristol-Myers Squibb, Olympus Corporation, Cardinal Health, MSD, Smith & Nephew, Kaken Pharmaceutical, Aska Pharmaceutical, Miyarisan Pharmaceutical, Toray Industries, Daiichi Sankyo Company, Chugai Foundation for Innovative Drug Discovery Science, Nippon Kayaku, EA Pharma, Intuitive Surgical, Takeda Pharmaceutical Company Limited, Sysmex Corporation, and Tsumura; and received educational grant from Chugai Pharmaceutical, Taiho Pharmaceutical, Yakult Honsha, Asahi Kasei Pharma, Otsuka Pharmaceutical, Ono Pharmaceutical, Tsumura, Kaken Pharmaceutical, Dainippon Sumitomo Pharma, EA Pharma, Eisai, Otsuka Pharmaceutical Factory, Kyowa Kirin, Takeda Pharmaceutical, Teijin Pharma, Nippon Covidien, Cardinal Health, and Kowa. All other authors declare that they have no relevant conflicts of interest., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Aims: Small common bile duct stones are known to occasionally clear spontaneously. This study aimed to prospectively assess the role of biliary stent placement in promoting the spontaneous clearance of small common bile duct stones., Methods and Results: We analyzed patients presenting with common bile duct stones of ≤5 mm diameter between June 2020 and May 2022. The exclusion criteria included asymptomatic patients, biliary pancreatitis, altered gastrointestinal anatomy, bile duct strictures (malignant or benign), and a history of EST. The biliary stents were inserted without stone removal. Stone clearance was assessed using endoscopic ultrasonography or endoscopic retrograde cholangiopancreatography after 3 months. Our primary endpoint was the clearance rate of common bile duct stones over 6 months, targeting a lower limit for the 95% confidence interval (CI) exceeding 25%. Of the 32 enrolled patients, 18 (56.3%; 95% CI: 37.7-73.6%) exhibited stone clearance. Early complications occurred in 11 patients (34.4%), totaling 12 incidents: acute cholecystitis in four, acute pancreatitis in three, biliary pain in three, and cholangitis in two patients. No severe complications occurred. Six (18.8%) patients experienced asymptomatic stent migration. Following stone clearance, four (12.5%) patients experienced stone recurrence, with an average duration of 256 ± 164 days., Conclusion: Biliary stenting appeared to effectively promote the clearance of small common bile duct stones in approximately half of the patients. However, the potential complications and risks of stone recurrence warrant close monitoring.This trial was registered in the Japan Registry of Clinical Trials (jRCT1042200020)., (© 2024 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Purpose: 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., Competing Interests: Masaki Tago is supported by grants from the Japan Society for the Promotion of Science, JSPS KAKENHI (Grant Number JP18K17322 and JP21H03166). Naoko E. Katsuki is supported by grants from the Japan Society for the Promotion of Science, JSPS KAKENHI (Grant Number JP23K16257). The authors report no other conflicts of interest in this work., (© 2024 Tago et al.)

Objectives: The 18- and 16-mm conduits in extracardiac total cavopulmonary connection (eTCPC) were reported to be optimal based on energy loss and flow stagnation at the relatively early phase. However, because the artificial conduit lacks growth potential, we have recently encountered some cases in which the conduit needs to be changed several years after eTCPC. These cases prompted us to reconsider the surgical strategy for eTCPC., Methods: We reviewed our 20-year single-centre experience with eTCPC patients (n = 256) to compare the 18-mm conduit (n = 195) and 16-mm conduit (n = 61) in terms of mortality and morbidity., Results: The 16-mm conduit was used significantly more frequently in patients whose main chamber was right ventricle (P < 0.001). There was also a significant difference in preoperative inferior vena cava pressure (P = 0.008). There was a significant difference in the actuarial rate of freedom from late-occurring complications, including mortality, between the 2 groups (P = 0.003). There was a significant difference in the actuarial rate of reoperation-free survival (P = 0.042); however, there was no significant difference in resurgical intervention for the conduit (P = 0.333). In multivariate analysis, preoperative inferior vena cava pressure was an independent predictor for late-occurring complications (hazard ratio 1.19; P = 0.026). Conduit size (18 or 16 mm) itself was not an independent predictive factor for late-occurring complications (P = 0.690)., Conclusions: The mid-term clinical outcomes in patients who underwent eTCPC were excellent with low mortality. Preoperative inferior vena cava pressure was the only predictive risk factor for postoperative morbidity, and the 16 mm conduit was not predictive thereof., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Aim: To clarify whether the Whitney Comorbidity Index (WCI) is useful in Asian adults with cerebral palsy (CP) and whether aspiration pneumonia and pressure ulcers improved the prognostic significance of the WCI., Method: This cohort study evaluated individuals aged at least 18 years with CP in Japan. We used Cox proportional hazards regression to analyse 2-year mortality rates. The predictive performance of the Charlson Comorbidity Index, Elixhauser Comorbidity Index, and WCI were compared as comorbidity assessment criteria. Aspiration pneumonia and pressure ulcers were added to the Cox models, and their impact on hazard ratios was determined., Results: Of the 2232 adults with CP, 72 died during the 2 years. The model with a previously reported weighted WCI with aspiration pneumonia and pressure ulcers produced the best fit. Additionally, the hazard risk of 2-year mortality for an unweighted WCI score of at least 4 was 2.56; when CP-specific comorbidities were added, it increased to 8.94., Interpretation: This study showed that the WCI can be used in Asian adults with CP. Furthermore, assessing patient age, aspiration pneumonia, and pressure ulcers in addition to the WCI increased the predictive value for mortality. Our findings indicate that the WCI can promote valid comparisons between international populations., What This Paper Adds: The Whitney Comorbidity Index (WCI) is useful among adults with cerebral palsy, irrespective of ethnic differences. Assessment of aspiration pneumonia and pressure ulcers increased the WCI predictive value. The WCI helps identify adults with cerebral palsy at risk of adverse outcomes., (© 2023 Mac Keith Press.)

Objective: Managing the risk of epileptic seizures in older adults is increasingly important as the population ages. Leukotriene receptor antagonists (LTRAs) are commonly used to treat asthma or allergic rhinitis. Preclinical studies suggest that LTRAs have antiepileptic effects; however, few population-based etiological studies on this topic have been available. Our study explored whether LTRAs reduce hospitalization risk associated with epileptic seizures in older individuals with asthma or allergic rhinitis., Methods: We conducted a new-user design analysis using the Shizuoka Kokuho database. We included all individuals aged 60-89 years who had at least one episode of allergic rhinitis or asthma during the study period. We compared individuals who newly started LTRAs with those who did not take LTRAs. Propensity score matching was used to balance the baseline characteristics of the participants. We compared the hazard ratios for seizure-related hospitalization between new LTRA users and non-users and performed subgroup analyses., Results: Our matched cohorts consisted of 64 724 new users and non-users of LTRAs who were aged 60-89 years and had asthma or allergic rhinitis. During the observation period, 377 (0.58%) and 595 (0.92%) incidents were observed in the LTRA new-user and non-user groups, respectively. The hazard ratio for seizure-related hospitalization was 0.75 (95% confidence interval [CI]: 0.62-0.92) in the LTRA new-user group compared with the non-user group. Subgroup analysis revealed that the hazard ratio was weak in diabetic patients (1.31; 95% CI: 0.72-2.38)., Significance: This study indicated that LTRAs reduced seizure-related hospitalization in older adult patients with allergic rhinitis or asthma. We could not evaluate the severity and related diseases of epileptic seizures during LTRAs. Further studies, including observational studies, detailed multicenter prospective studies, and clinical trials, are needed to validate these findings., Plain Language Summary: This study examined if leukotriene receptor antagonists (LTRAs), commonly used for asthma or allergies, could lower seizure risk in older adults. Analyzing health records of 60-89 year-olds with asthma or allergies, we found a reduced rate of seizure-related hospitalizations in those starting LTRAs, though this was not as evident in diabetic patients. Our results suggest potential benefits of LTRAs in preventing seizures in older adults with respiratory issues, but further research is needed to confirm these findings., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Purpose: The purpose of this study was to evaluate the changes in membranous septum (MS) length during the cardiac cycle and by measurement methods using the preoperative computed tomography (CT) images for transcatheter aortic valve replacement (TAVR)., Method: Among 34 consecutive patients who underwent preoperative contrast-enhanced CT for TAVR, we measured MS lengths by three measurement methods (coronal, stretched, and reformatted coronal view method) at 10% intervals in the cardiac cycle., Result: MS lengths differed between the three measurement methods in all cardiac phases. Moderate correlations were observed between the MS lengths measured by the coronal view method and the other two methods. In contrast, strong correlations were observed between the MS lengths measured by the stretched view method and the reformatted coronal view method. The frequencies of the minimum and maximum MS lengths during the cardiac cycle tended to be highest at R-R 90% and R-R 30%, respectively. The median MS lengths at R-R 90% were smaller than those at R-R 30% in all measurement methods., Conclusion: The MS length in patients undergoing contrast-enhanced CT for TAVR varies notably depending on the cardiac cycle and measurement methods. When evaluating MS length, it is crucial to consider the measurement method and to perform measurements during diastole in order to evaluate the minimum value during the cardiac cycle.

This study investigated which conditions could be used to identify patients with chronic myeloid leukemia (CML) from a National Health Insurance claims dataset. During April 2012 and September 2018, 1,789,462 employees were enrolled in the dataset for Shizuoka Prefecture residents. The number of patients with the ICD-10 code for CML was 761. Among them, 246 who had been prescribed a tyrosine kinase inhibitor were considered as having true CML. The positive predictive value was calculated as 32.3% when CML was identified by ICD-10 code alone. Combination of ICD-10 code with prescribed drugs was required to accurately identify patients with CML from the insurance database.

Purpose: To elucidate the risk factors associated with the onset of glioblastoma (GBM) utilizing a comprehensive administrative claims database from a major governmental district in Japan., Methods: Using the Shizuoka Kokuho Database (SKDB) for the period from April 2012 to September 2021, we conducted a retrospective analysis of 1,465,353 participants, identifying GBM cases using specific Japanese disease codes in conjunction with associated treatments. Risk factors were assessed using both univariable and multivariable Cox proportional hazards models., Results: Within the cohort, 182 participants (0.012%) received a GBM diagnosis during the study period, resulting in an incidence rate of 2.1 per 100,000 person-years. The multivariable analysis revealed that older age, male sex, and peripheral vascular disease (PVD) significantly influenced the risk of GBM onset. No clear link was found between allergic conditions and GBM risk, in contrast to some previous research., Conclusion: Employing a robust health insurance database, this study revealed significant associations between GBM and factors such as age, male sex, and PVD within the Japanese population. It provides key insights into GBM epidemiology and underscores the potential of health insurance databases for large-scale oncological research., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The coronavirus disease 2019 (COVID-19) pandemic has dramatically changed because of virus mutations, vaccine dissemination, treatment development and policies, among other factors. These factors have a dynamic and complex effect on the characteristics and outcomes of patients. Therefore, there is an urgent need to understand those changes and update the evidence. We used a large-scale real-world data set of 937,758 patients with COVID-19 from a nationwide claims database that included outpatients and inpatients in Japan to investigate the changes in their characteristics, outcomes and risk factors for severity/mortality from the early pandemic to the delta variant-predominant waves. The severity of COVID-19 was defined according to the modified World Health Organization clinical-progression ordinal scale. With changing waves, mean patient age decreased, and proportion of patients with comorbidities decreased. The incidences of "severe COVID-19 or death (i.e. ≥severe COVID-19)" and "death" markedly declined (5.0% and 2.9%, wild-type-predominant; 4.6% and 2.2%, alpha variant-predominant and 1.4% and 0.4%, delta variant-predominant waves, respectively). Across the wave shift, risk factors for ≥ severe COVID-19 and death, including older age, male, malignancy, congestive heart failure and chronic obstructive pulmonary disease, were largely consistent. The significance of some factors, such as liver disease, varied as per the wave. This study, one of the largest population-based studies on COVID-19, showed that patient characteristics and outcomes changed during the waves. Risk factors for severity/mortality were similar across all waves, but some factors were inconsistent. These data suggest that the clinical status of COVID-19 will change further with the coming epidemic wave.

Background: Although tranexamic acid (TXA) has occasionally been used to prevent postoperative recurrence of chronic subdural hematoma (CSDH) after burr hole craniotomy (BC), robust evidence of its efficacy has been lacking., Objective: To assess the efficacy and safety of postoperative oral administration of TXA after BC for CSDH among the elderly., Methods: This retrospective, propensity score-matched cohort study was carried out with a large Japanese local population-based longitudinal cohort in the Shizuoka Kokuho Database between April 2012 and September 2020. Patients included were age 60 years or older and had undergone BC for CSDH but were not undergoing dialysis. Covariates were collected from records of the preceding 12 months from the month of first BC, and patients were followed up for 6 months after surgery. The primary outcome was repeat surgery, and the secondary outcome was death or the onset of thrombosis. Data on postoperative TXA administration were collected and compared with controls using propensity score matching., Results: Of the 8544 patients who underwent BC for CSDH, 6647 were included, with 473 placed in the TXA group and 6174 placed in the control group. After 1:1 matching, repeated BC was found to have been performed in 30 of 465 patients (6.5%) in the TXA group and in 78 of 465 patients (16.8%) in the control group (relative risk, 0.38; 95% CI, 0.26-0.56). No significant difference was observed for death or the onset of thrombosis., Conclusion: Oral administration of TXA reduced the occurrence of repeat surgery after BC for CSDH., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Outpatient nutritional counseling by a registered dietitian is often performed to prevent weight loss, but evidence supporting this practice is insufficient. In this study, we aimed to clarify the effectiveness of four-time outpatient nutritional counseling in weight-loss prevention compared with conventional intervention limited to one-time nutritional counseling. This study was designed as a retrospective cohort study. The target population was postoperative patients with stage IA and IB gastric cancer. Groups that received one-time and four-time nutritional counseling included patients who underwent gastrectomy from May 2014 to April 2017 and May 2017 to December 2019, respectively. The one-time group received counseling at discharge; the four-time group received counseling at discharge, at the first outpatient visit, and at 3 and 6 months postoperatively. There were 58 patients in the one-time group and 27 patients in the four-time group, with a significant difference in length of hospital stay (p = 0.042). Thirty-six patients (62.1%) in the one-time nutritional counseling group and 12 (44.4%) in the four-time group had a weight loss of 5% or more from hospital discharge to 6 months postoperatively. The adjusted risk ratio for the effectiveness of four counseling sessions compared with one session was 0.69 (95% confidence interval 0.35-1.34). In subgroup analysis, the effect of nutritional guidance was greater for patients with body mass index ≥23 kg/m2, but this depended on the outcome and number of cases, and there was no essential difference between the groups. In postoperative patients with stage IA and stage IB gastric cancer, four sessions of outpatient nutrition counseling may be not superior to one counseling session in preventing weight loss., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Matsushita 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 While several predictive models for falls have been reported such as we reported in 2020, those for fall "injury" have been unreported. This study was designed to develop a model to predict fall injuries in adult inpatients using simple predictors available immediately after hospitalization. MATERIAL AND METHODS This was a single-center, retrospective cohort study. We enrolled inpatients aged ≥20 years admitted to an acute care hospital from April 2012 to March 2018. The variables routinely obtained in clinical practice were compared between the patients with fall injury and the patients without fall itself or fall injury. Multivariable analysis was performed using covariables available on admission. A predictive model was constructed using only variables showing significant association in prior multivariable analysis. RESULTS During hospitalization of 17 062 patients, 646 (3.8%) had falls and 113 (0.7%) had fall injuries. Multivariable analysis showed 6 variables that were significantly associated with fall injuries during hospitalization: age (P=0.001), sex (P=0.001), emergency transport (P<0.001), medical referral letter (P=0.041), history of falls (P=0.012), and abnormal bedriddenness ranks (all P≤0.001). The area under the curve of this predictive model was 0.794 and the shrinkage coefficient was 0.955 using the same data set given above. CONCLUSIONS We developed a predictive model for fall injuries during hospitalization using 6 predictors, including bedriddenness ranks from official Activities of Daily Living indicators in Japan, which were all easily available on admission. The model showed good discrimination by internal validation and promises to be a useful tool to assess the risk of fall injuries.

Purpose: To investigate the clinical practices of diagnosing multicystic cervical lesions as a means to develop a more appropriate diagnostic algorithm for gastric-type adenocarcinoma (GAS) and its precursors., Methods: Clinical information for 159 surgically treated patients for multicystic disease of the uterine cervix was collected from 15 hospitals. We performed a central review of the MRI and pathological findings. The MRI findings were categorized into four types including two newly proposed imaging features based on the morphology and distribution of cysts, and the diagnosis accuracy was assessed. Among the four MRI types, types 1 and 2 were categorized as benign lesions that included LEGH; type 3 were precancerous lesions (with an assumption of atypical LEGH); and type 4 were malignant lesions., Results: The central pathological review identified 56 cases of LEGH, seven with GAS, four with another form of carcinoma, and 92 with benign disease. In clinical practice, over-diagnosis of malignancy (suspicion of MDA) occurred for 12/19 cases (63.2%) and under-diagnosis of malignancy occurred for 4/11 (36%). Among the 118 patients who had a preoperative MRI and underwent a hysterectomy, type 3 or 4 MRI findings in conjunction with abnormal cytology were positively indicative of premalignancy or malignancy, with a sensitivity and specificity of 61.1% and 96.7%, respectively., Conclusions: Although the correct preoperative diagnosis of cervical cancer with a multicystic lesion is challenging, the combination of cytology and MRI findings creates a more appropriate diagnostic algorithm that significantly improves the diagnostic accuracy for differentiating benign disease from premalignancy and malignancy., (© 2023. The Author(s).)

Introduction: Acquired haemophilia A (AHA) is a rare disease. The risk factors have yet to be studied., Aim: We aimed to identify risk factors for late-onset AHA in Japan., Methods: A population-based cohort study was conducted using data from the Shizuoka Kokuho Database. The study population was defined as individuals aged ≥60 years. Cause-specific Cox regression analysis was performed to calculate hazard ratios., Results: Of 1,160,934 registrants, there were 34 patients with newly diagnosed AHA. The mean follow-up period was 5.6 years, and the incidence of AHA was 5.21 per million person-years. Myocardial infarction, diabetes mellitus, solid tumors, antimicrobial agents, phenytoin and anti-dementia drugs, which showed significant differences in the univariate analysis, were excluded from the multivariable analysis because of the small number of cases. Multivariable regression analysis showed that the presence of Alzheimer's disease (hazard ratio [HR]:4.28, 95% confidence interval [CI]:1.67-10.97) and rheumatic disease (HR:4.65, 95% CI:1.79-12.12) increased the risk of AHA development., Conclusion: We found that comorbid Alzheimer's disease is a risk factor of AHA incidence in the general population. Our findings provide insight into the etiology of AHA, and the proof of the coexistence of Alzheimer's disease may support the recent notion that Alzheimer disease is an autoimmune disease., (© 2023 John Wiley & Sons Ltd.)

Background: Hydrochlorothiazide (HCT), a widely used hypertensive drug, has photocarcinogenic potential, leading to concerns about the development of nonmelanoma skin cancers (SCs) after intake. Despite substantial numbers of observational studies, the results remain inconsistent especially among Asian countries., Objective: To assess the incidence of nonmelanoma SCs in hypertensive Japanese HCT users compared with nonusers., Methods: A population-based, cohort nested, propensity score-matched study was conducted using the Shizuoka Kokuho database. All participants were patients aged ≥60 years. Hazard ratios for SC incidence were calculated in the matched cohorts using the propensity scores of potential confounders, sex, age category, comorbidities, and administration of methotrexate, cyclosporin, and statins., Results: The risk of SC was higher in HCT users than in nonusers (hazard ratio, 1.58; 95% confidence interval, 1.04-2.40), with preferential sun-exposed location and a tendency to develop squamous cell carcinoma, but not basal cell carcinoma or Bowen disease., Limitations: No additional information was available from other than medical records. The data were confined to a Japanese population., Conclusion: HCT use increases the risk of SC in Japanese patients with hypertension and a dark skin type, highlighting the increased risk of SC among HCT users in the aging society worldwide., Competing Interests: None disclosed., (© 2023 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Hip fractures are common in patients of advanced age and are associated with excess mortality. Rapid and accurate prediction of the prognosis using information that can be easily obtained before surgery would be advantageous to clinical management. We performed a population-based retrospective cohort study using an 8.5-year Japanese claims database (April 2012-September 2020) to develop and validate a predictive model for long-term mortality after hip fracture. The study included 43,529 patients (34,499 [79.3%] women) aged ≥65 years with first-onset hip fracture. During the observation period, 43% of the patients died. Cox regression analysis identified the following prognostic predictors: sex, age, fracture site, nursing care certification, and several comorbidities (any malignancy, renal disease, congestive heart failure, chronic pulmonary disease, liver disease, metastatic solid tumor, and deficiency anemia). We then developed a scoring system called the Shizuoka Hip Fracture Prognostic Score (SHiPS); this system was established by scoring based on each hazard ratio and classifying the degree of mortality risk into four categories based on decision tree analysis. The area under the receiver operating characteristic (ROC) curve (AUC) (95% confidence interval [CI]) of 1-year, 3-year, and 5-year mortality based on the SHiPS was 0.718 (95% CI, 0.706-0.729), 0.736 (95% CI, 0.728-0.745), and 0.758 (95% CI, 0.747-0.769), respectively, indicating good predictive performance of the SHiPS for as long as 5 years after fracture onset. Even when the SHiPS was individually applied to patients with or without surgery after fracture, the prediction performance by the AUC was >0.7. These results indicate that the SHiPS can predict long-term mortality using preoperative information regardless of whether surgery is performed after hip fracture., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Background: Acute kidney injury (AKI) is a globally critical issue. Most studies about AKI have been conducted in limited settings on perioperative or critically ill patients. As a result, there is little information about the epidemiology and risk factors of AKI in the general population., Methods: We conducted a population-based cohort study using the Shizuoka Kokuho Database. We included subjects with records of health checkup results. The observation period for each participant was defined as from the date of insurance enrollment or April 2012, whichever occurred later, until the date of insurance withdrawal or September 2020, whichever was later. Primary outcome was AKI associated with admission based on the ICD-10 code. We described the incidence of AKI and performed a multivariate analysis using potential risk factors selected from comorbidities, medications, and health checkup results., Results: Of 627,814 subjects, 8044 were diagnosed with AKI (incidence 251 per 100,000 person-years). The AKI group was older, with more males. Most comorbidities and prescribed medications were more common in the AKI group. As novel factors, statins (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.80-0.89) and physical activity habits (HR 0.79, 95% CI 0.75-0.83) were associated with reduced incidence of AKI. Other variables associated with AKI were approximately consistent with those from previous studies., Conclusions: The factors associated with AKI and the incidence of AKI in the general Japanese population are indicated. This study generates the hypothesis that statins and physical activity habits are novel protective factors for AKI., (© 2022. The Author(s).)

Background/aim: Malnutrition, immune deficiency, and skeletal muscle loss are associated with a risk of postoperative complications in patients with various types of cancer. This study evaluated whether malnutrition, immunological deficiencies, and skeletal muscle loss during neoadjuvant chemotherapy (NAC) predict postoperative complications in patients with esophageal cancer., Patients and Methods: We retrospectively reviewed 123 patients with esophageal squamous cell carcinoma treated with NAC and esophagectomy at our hospital between 2014 and 2019. Patients were divided into two groups based on the presence or absence of postoperative infectious complications, such as pneumonia, anastomotic leakage, surgical site infections, pyothorax, acalculous cholecystitis, and peripheral phlebitis. Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and Onodera prognostic nutritional index were used as indicators of systemic inflammation and nutritional status. Skeletal muscle mass was evaluated using the skeletal muscle index (SMI), calculated by evaluating the total cross-sectional area of muscle tissue at the third lumbar level in computed tomography imaging. Univariable and multivariable logistic regression analyses were used to identify predictors of postoperative infectious complications., Results: Postoperative infectious complications occurred in 41 patients (33.3%). A reduction in SMI was observed in 105 patients (87.8%) during NAC. Univariable and multivariable analyses indicated that the reduction in SMI during NAC was an independent predictor of postoperative complications (odds ratio=0.89; 95% confidence interval=0.79-0.99; p=0.048)., Conclusion: Skeletal muscle loss during NAC is a useful predictor of postoperative complications in patients with esophageal cancer undergoing esophagectomy., Competing Interests: The Authors have no conflicts of interest to declare in relation to this study., (Copyright 2023, International Institute of Anticancer Research.)

Background: Asthma cases have been increasingly investigated using claims data. However, the validity of defining asthma cases using health insurance claims in Japan is unclear. This study aims to assess the positive and negative predictive values of our proposed discrimination criteria for asthma., Methods: We developed discrimination criteria for asthma based on both the International Statistical Classification of Diseases and Related Health Problems (ICD)-10 disease codes for asthma and health insurance claims data for prescriptions and the treatment of asthma. Inclusion criteria were patients aged ≥16 years with at least one health insurance claim from April 2018 to March 2019 in all departments of our hospital. Physician-diagnosed asthma documented in the charts was used as the reference standard. Positive and negative predictive values of the discrimination criteria for physician-diagnosed asthma were estimated and compared with those estimated from discrimination criteria based solely on ICD-10 codes., Results: The new discrimination criteria had a high positive predictive value (PPV) of 86.0%, which was significantly higher than the PPV for the criteria defined solely by the ICD-10 codes (61.5%) (P < 0.01). The negative predictive values for both criteria were 100%. Allergic rhinitis and chronic cough were frequently misclassified as asthma using the discrimination criteria based solely on ICD-10 codes but were more likely to be appropriately classified using our proposed criteria., Conclusions: Our proposed criteria adequately identified asthma subjects using health insurance claims data in Japan with a high PPV. Further studies are needed for external validation of these criteria., (Copyright © 2022 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background: The American Society of Anesthesiologists-Physical Status (ASA-PS) classification system has been shown to predict morbidity and mortality after surgery. However, the impact of the ASA-PS on esophageal cancer treatment remains unclear. This study examined both the impact of the ASA-PS on treatment, including surgery and perioperative chemotherapy, and the prognostic effects of ASA-PS class in patients who had undergone esophagectomy for thoracic esophageal cancer or esophagogastric junction cancer., Methods: ASA-PS status was collected for 301 patients who had undergone esophagectomy between January 2007 and June 2016 for thoracic esophageal cancer or esophagogastric junction cancer at a single institution. As the ASA-PS was updated in 2014, the previous classifications of all patients were reevaluated using the updated standard by a surgeon with the previous classifications masked. The dose intensity of preoperative chemotherapy was also compared across classes. Multivariate Cox regression analysis was used to analyze the association between ASA-PS class and overall survival., Results: Patients whose reevaluations had placed them in a more severe ASA-PS class showed significantly poorer overall and cancer-specific survival rates. The dose intensities of cisplatin and 5-fluorouracil for preoperative chemotherapy were significantly lower in patients in the more severe ASA-PS classes. Multivariate analysis showed that ASA-PS class was an independent prognostic factor for overall survival., Conclusion: Preoperative ASA-PS classification may influence the intensity of perioperative treatment and may be a valuable long-term prognostic factor for patients with esophageal cancer undergoing esophagectomy., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Several reliable predictive models for falls have been reported, but are too complicated and time-consuming to evaluate. We recently developed a new predictive model using just eight easily-available parameters including the official Japanese activities of daily living scale, Bedriddenness ranks, from the Ministry of Health, Labour and Welfare. This model has not yet been prospectively validated. This study aims to prospectively validate our new predictive model for falls among inpatients admitted to two different hospitals., Methods: A double-centered prospective cohort study was performed from October 1, 2018, to September 30, 2019 in an acute care hospital and a chronic care hospital. We analyzed data from all adult inpatients, for whom all data required by the predictive model were evaluated and recorded. The eight items required by the predictive model were age, gender, emergency admission, department of admission, use of hypnotic medications, previous falls, independence of eating, and Bedriddenness ranks. The main outcome is in-hospital falls among adult inpatients, and the model was assessed by area under the curve., Results: A total of 3,551 adult participants were available, who experienced 125 falls (3.5%). The median age (interquartile range) was 78 (66-87) years, 1,701 (47.9%) were men, and the incidence of falls was 2.25 per 1,000 patient-days and 2.06 per 1,000 occupied bed days. The area under the curve of the model was 0.793 (95% confidence interval: 0.761-0.825). The cutoff value was set as - 2.18, making the specificity 90% with the positive predictive value and negative predictive value at 11.4% and 97%., Conclusions: This double-centered prospective cohort external validation study showed that the new predictive model had excellent validity for falls among inpatients. This reliable and easy-to-use model is therefore recommended for prediction of falls among inpatients, to improve preventive interventions., Trial Registration: UMIN000040103 (2020/04/08)., (© 2022. The Author(s).)

Background: Approximately 7-20% of patients with herpes zoster (HZ) develop zoster-associated pain (ZAP). ZAP not only impairs quality of life and psychological well-being, but also can reduce work effectiveness, which has negative economic effects. Reports of ZAP risk factors are inconsistent., Objective: To confirm risk factors for the development of severe ZAP in HZ patients in Japan using a large-scale database, the Shizuoka Kokuho Database., Methods: A population-based cohort study using the Shizuoka Kokuho Database was conducted. Of 792,647 patients, 7491 (0.95%) experienced "severe ZAP" (as defined in this study). We developed a ZAP risk prediction scoring system by identifying risk factors using logistic regression analysis of several candidate risk factors for severe ZAP: age, sex, seasonality, and presence of comorbidities (using the Charlson comorbidity index), excluding HIV/AIDS., Results: We identified peripheral vascular disease and the onset from October to December as novel risk factors for severe ZAP, in addition to the previously reported risk factors of age and comorbidities (cerebral vascular disease, chronic pulmonary disease, rheumatic disease, peptic ulcer, liver disease, diabetes, and malignant neoplasms with/without metastasis). In contrast, dementia was found to reduce ZAP risk. We developed a susceptibility index to predict the risk of ZAP., Conclusion: We newly demonstrated that peripheral vascular disease and the onset from October to December are ZAP risk factors. Our comorbidity findings support previous observations. The susceptibility index proposed here provides a new approach to the prevention of ZAP using early intervention for high-risk patients., Competing Interests: Conflict of interest No conflict of interest was declared., (Copyright © 2022 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Introduction: Average dialysis vintage in Japan is among the longest in the world, providing a unique opportunity to characterize pregnancy under conditions of long dialysis vintage. In 2017, we carried out a nationwide survey following up on a similar survey in 1996, in which we investigated the prevalence and outcomes of pregnancy in women undergoing dialysis and assessed risk factors associated with neonatal and maternal complications., Methods: The target population was women aged 15-44 years undergoing maintenance dialysis between 2012 and 2016. The survey was conducted in 2693 dialysis units., Results: A response was obtained from 951 dialysis units, yielding a target population of 1992 women of childbearing age receiving hemodialysis or peritoneal dialysis. Pregnancy occurred only among women receiving hemodialysis, with 25 pregnancies (1.26% in 5 years) being reported for 20 women. Detailed information about 19 pregnancies (mean age 34.6 ± 5.7 years at conception, mean dialysis vintage 8.4 ± 7.3 years) indicated 4 spontaneous abortions, 1 elective abortion, no neonatal deaths, and 14 surviving infants, including 5 full-term (≥ 37 weeks at birth), 2 late preterm (34-36), and 3 extremely preterm (< 28) cases. Neonatal complications occurred in the offspring of 3 mothers who had end-stage renal disease (ESRD) caused by primary glomerulonephritis and serum albumin levels (sAlb) ≤ 3.2 mg/dL in the first trimester. These mothers had started dialysis at 12, 17, and 30 years of age. ESRD caused by diabetic nephropathy or primary glomerulonephritis, age at conception ≥ 38 years, and sAlb ≤ 3.2 mg/dL were associated with maternal complications, although not significantly., Conclusions: In this study, the pregnancy rate of Japanese women with ESRD was 0.25% per year. The study generates the hypothesis that ESRD caused by diabetic nephropathy and age at conception ≥ 38 years are potential risk factors for maternal complications but not for neonatal complications in dialysis patients, and that hypoalbuminemia is a potential risk factor for both kinds of complications., (© 2021. The Author(s).)

Objective: The incidence of type 1 diabetes mellitus (T1DM) and hypothyroidism as immune-related adverse events (irAEs) after programmed cell death-1 inhibitor (PD-1i) administration has not yet been sufficiently evaluated in a real clinical setting. To assess the incidence of T1DM and hypothyroidism among PD-1is and to identify the risk factors associated with hypothyroidism using a large claims database., Methods: This cohort study used the Shizuoka Kokuho database in Japan from 2012 to 2018, including approximately 2.2 million people. We enrolled 695 PD-1i-treated patients. T1DM and hypothyroidism as irAEs were identified using International Classification of Diseases 10th Revision and Anatomical Therapeutic Chemical classification codes. Risk factors for hypothyroidism were explored using the multivariable Fine and Gray regression model after adjusting for age group and sex, treating death as a competing risk., Results: The cumulative incidences of T1DM and hypothyroidism were 0.3% and 8.3%, respectively. We described the detailed onset timing of irAEs in patients with T1DM and hypothyroidism; hypothyroidism was observed evenly within 1 year of the PD-1i prescription. Sex and certain cancer types, such as lung and urothelial cancers, were significantly associated with subdistribution hazard ratio (sHR) (female: sHR, 2.04 [95% CI, 1.20-3.47]; lung cancer: sHR, 0.55 [95% CI, 0.32-0.95]; and urothelial carcinoma: sHR, 2.40 [95% CI, 1.05-5.49])., Conclusion: The incidence of T1DM and hypothyroidism as irAEs and associated risk factors identified in this analysis were comparable to those found in previous studies. The use of a large claims database to detect irAEs, such as T1DM and hypothyroidism, may lead to safer use of PD-1is., (Copyright © 2020 AACE. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Multi-regional clinical trials (MRCTs) are an efficient drug development strategy for eliminating drug lag in East Asian countries. In planning MRCTs according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use E17 guideline, it is expected that East Asian populations with relatively similar ethnicity can be pooled as one population. However, evidence supporting this assumption is limited. This study aimed to investigate population/regional differences considering influencing factors among East Asian regions using MRCT data as a research model., Methods: A retrospective analysis was conducted to determine the efficacy of two drugs, asenapine, a schizophrenia drug, and tadalafil, a dysuria drug for benign prostatic hyperplasia, using MRCT data from Japan, Korea, and Taiwan. First, predictive factors and effect modifiers were evaluated. Then, population/regional differences were evaluated using multivariate regression models, with the interaction term Region-by-Treatment group and adjustment for influencing intrinsic/extrinsic factors., Results: Among the 4 outcomes for the two drugs, no significant population/regional differences were detected (P > 0.05) by the adjusted regression models. The effect modifiers, such as pretreatment drug status or concurrent diseases, were common among countries., Conclusions: No significant population/regional efficacy differences were found for the two drugs among the three regions. This finding supported the possible applicability of the region pooling strategy for MRCTs in East Asia, emphasizing the benefits of exploring ethnic difference/influencing factors at an early stage to design further confirmatory studies. However, further evidence for various drugs should be accumulated.

Background: The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in preventing pneumococcal pneumonia has been controversial., Methods: To evaluate the effectiveness of the PPSV23 in elderly outpatients with chronic respiratory diseases, we carried out a case-control study, including 4128 outpatients aged ≥ 65 years, in the respiratory department., Results: There were 320 vaccinated patients, of which 164 were diagnosed with pneumococcal pneumonia. The adjusted odds ratio was 0.39 (95% confidence interval (CI), 0.17 to 0.89). In the subsets consisting of age groups ≥ 70 and ≥ 75 years, the adjusted odds ratio (95% CI) was respectively 0.16 (0.04 to 0.67) and 0.15 (0.02 to 1.12)., Conclusion: This real-world study suggests that PPSV23 can be useful in preventing pneumococcal pneumonia in the elderly with chronic respiratory diseases.

Background: The statistical validities of the official Japanese classifications of activities of daily living (ADLs), including bedriddenness ranks (BR) and cognitive function scores (CFS), have yet to be assessed. To this aim, we evaluated the ability of BR and CFS to assess ADLs using inter-rater reliability and criterion-related validity., Methods: New inpatients aged ≥75 years were enrolled in this hospital-based prospective observational study. BR and CFS were assessed once by an attending nurse, and then by a social worker/medical clerk. We evaluated inter-rater reliability between different professions by calculating the concordance rate, kappa coefficient, Cronbach's α, and intraclass correlation coefficient. We also estimated the relationship of the Barthel Index and Katz Index with the BR and CFS using Spearman's correlation coefficients., Results: For the 271 patients enrolled, BR at the first assessment revealed 66 normal, 10 of J1, 15 of J2, 18 of A1, 31 of A2, 37 of B1, 35 of B2, 22 of C1, and 32 of C2. The concordance rate between the two BR assessments was 68.6%, with a kappa coefficient of 0.61, Cronbach's α of 0.91, and an intraclass correlation coefficient of 0.83, thus showing good inter-rater reliability. BR was negatively correlated with the Barthel Index (r = - 0.848, p < 0.001) and Katz Index (r = - 0.820, p < 0.001), showing justifiable criterion-related validity. Meanwhile, CFS at the first assessment revealed 92 normal, 47 of 1, 19 of 2a, 30 of 2b, 60 of 3a, 8 of 3b, 8 of 4, and 0 of M. The concordance rate between the two CFS assessments was 70.1%, with a kappa coefficient of 0.62, Cronbach's α of 0.87, and an intraclass correlation coefficient 0.78, thus also showing good inter-rater reliability. CFS was negatively correlated with the Barthel Index (r = - 0.667, p < 0.001) and Katz Index (r = - 0.661, p < 0.001), showing justifiable criterion-related validity., Conclusions: BR and CFS could be reliable and easy-to-use grading scales of ADLs in acute clinical practice or large-scale screening, with high inter-rater reliabilities among different professions and significant correlations with well-established, though complicated to use, instruments to assess ADLs., Trial Registration: UMIN000041051 (2020/7/10).

Background: Evidence of factors associated with psoriasis from large population-based cohort studies is scarce., Objective: We aimed to explore the risk factors of late-onset psoriasis., Methods: This study included 487,835 Japanese participants aged 40-107 years, who were followed prospectively from 2012 to 2018 using individually linked databases between annual health checkups and medical claims., Results: During the study period, 2793 patients (0.57%) newly developed psoriasis; 13.8% had moderate-to-severe psoriasis. In the multivariate analysis, factors associated with psoriasis onset were age (hazard ratio [HR] 1.11 {95% confidence interval [CI]: 1.06-1.16}), male sex (HR: 1.11 [95% CI: 1.02-1.21]), body mass index (HR: 1.09 [95% CI: 1.05-1.14]), smoking (HR: 1.46 [95% CI: 1.31-1.63]), not exercising ≥1 hour per week (HR: 1.13 [95% CI: 1.05-1.22]), and gamma-glutamyl transpeptidase (HR: 1.04 [95% CI: 1.01-1.06]). When we used weight increment of ≥10 kg since the age of 20 years instead of body mass index in the multivariate model, this was also a risk factor (HR: 1.12 [95% CI: 1.04-1.21])., Limitations: This study targeted people aged >40 years, thereby narrowing the search to the risk factors of late-onset psoriasis., Conclusion: We showed that increasing age, male sex, body mass index, smoking, low physical activity, weight gain, and gamma-glutamyl transpeptidase are associated with late-onset development of psoriasis and revealed a relationship between liver dysfunction and psoriasis development., (© 2020 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Grade 3 (G3, poorly differentiated) is an important treatment-decision factor in stage II colon cancer, but no unified diagnostic criteria are established. According to previous studies, an intratumoural poorly differentiated area with no glandular formation (POR) that fills the microscopic field of a ×40 objective lens was an essential factor that defined G3. We aimed to prospectively validate this in a randomized controlled study of adjuvant chemotherapy (SACURA trial). We enrolled 991 patients with stage II colon cancer. POR was graded according to the ×40 objective lens rule and the intensity of poorly differentiated clusters (Grade), and its prognostic power was compared with that of the conventional tumor grade on the basis of predominant histology rule (Grade). According to Grade, 313, 526, and 152 tumors were classified as G1, G2, and G3, respectively, and the 5-year relapse-free survival (RFS) rates were 91.1%, 82.9%, and 74.7%, respectively (P<0.0001). When G3 and G3 were alternatively added to the prognostic model consisting of 8 conventional factors, only G3 was a significant factor for RFS (P=0.040, Wald test). The adverse impact of G3 on RFS was greater in the microsatellite stable/microsatellite instability-low subset than that in the full analysis set. In the microsatellite stable/microsatellite instability-low subset, the 5-year RFS rate of patients with G3 tumors in the chemotherapy group achieved greater improvement (9.1%) than the surgery-alone group. The least differentiation policy with the ×40 objective lens rule may be highlighted as the diagnostic criterion for G3 because of its validated prognostic value.

Background: Although an anastomotic leak after esophagectomy is one of the most common postoperative complications, it is not well understood whether specific anatomic factors of the different route of reconstruction can predispose to the development of anastomotic leak after esophagectomy. This study aimed to clarify whether various factors related to the size of the thoracic inlet are independent predictors of anastomotic leak after esophagectomy., Methods: We reviewed 248 patients who underwent esophagectomy with retrosternal reconstruction of the gastric conduit between January 2013 and March 2019. Various factors related to the size of the thoracic inlet were measured using computed tomography. Multivariate logistic regression was used to analyze the association between various measurements and anastomotic leak., Results: Anastomotic leak occurred in 38 patients (15.3%). On univariate analysis, the thickness of the sternum, the thickness of the clavicle, the sternum-trachea distance, the ratio of the sternum-trachea distance/sternum-vertebral body distance, sex, body mass index, and method of anastomosis were statistically significantly associated with anastomotic leak. On multivariate analysis, the ratio of the sternum-trachea distance/sternum-vertebral body distance and the method of anastomosis were the independent risk factors for anastomotic leak., Conclusion: The ratio of the sternum-trachea distance/sternum-vertebral body distance is associated with cervical anastomotic leak after retrosternal gastric conduit reconstruction after esophagectomy. Measurement of the thoracic inlet space may contribute to preoperative planning, such as for the route of the conduit for reconstruction and anastomotic site., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Adjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC), a randomised phase III trial, demonstrated that adjuvant therapy with S-1 for stage III colon cancer was non-inferior in 3-year disease-free survival (DFS) to that of tegafur-uracil plus leucovorin (UFT/LV). We updated DFS and overall survival (OS) and performed T x N subset analysis., Methods: A total of 1518 patients with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80-120  mg/day on days 1-28 every 42 days, four courses) or UFT/LV (UFT: 300-600  mg/day and LV: 75  mg/day on days 1-28 every 35 days, five courses)., Results: The 5-year DFS rates of the S-1 and UFT/LV group were 70.2 % and 66.9 %, respectively (HR 0.88; 95%  CI 0.74 to 1.06; p=0.177), and non-inferiority of DFS was reconfirmed with a median of 63.5-month follow-up. The similarity of OS was also confirmed (HR 0.92; 95%  CI 0.72 to 1.17; p=0.488); 5-year OS rates of the S-1 and UFT/LV group were 86.0 % and 84.4 %, respectively. No significant interactions were identified between the major baseline characteristics and DFS of the S-1 and UFT/LV groups, except for histological type; S-1 was more favourable in patients with poorly differentiated adenocarcinoma. Patient outcomes were well separated by TNM-substages (IIIA/IIIB/IIIC). With the patients divided into 20 subsets by T and N factors, the DFS and OS rates of T3 and N1 subset, which accounted for 62 % of stage IIIB patients and 44 % of all studied subjects, were significantly better than those of the other subsets in stage IIIB and similar to those of stage IIIA., Conclusions: Adjuvant therapy of S-1 for stage III colon cancer was reconfirmed to be non-inferior in DFS to those of UFT/LV after long follow-up. No difference in OS was also demonstrated. T3N1 patients might be considered separately from other patients included in stage IIIB because of its favourable outcome., Trial Registration Number: NCT00660894., Competing Interests: Competing interests: MI has received honoraria from Taiho Pharmaceutical Co. Ltd., and Merck Serono Co. Ltd.; research funding from Taiho and Yakult Honsha Co. Ltd. KS received honoraria and research funding from Taiho Pharmaceutical Co. Ltd. and Chugai Pharmaceutical Co. Ltd. All remaining authors have declared no conflicts of interest.

Background: The pathogenesis of aspirin-exacerbated respiratory disease (AERD) is characterized by the low expression of cyclooxygenase-2 (COX-2) in airway epithelia, which decreases the production of prostaglandin E 2 (PGE 2 ). Conversely, cigarette smoke stimulates COX-2 expression in airway epithelia. Therefore, it was hypothesized that the development of AERD would be suppressed by elevated PGE 2 levels in smokers, and smoking cessation might increase susceptibility to AERD., Objective: The objective of this study was to evaluate the relationship between smoking and the risk of AERD development., Methods: The smoking status of patients with AERD (n = 114) was compared with 2 control groups with aspirin-tolerant asthma (ATA), patients diagnosed by a systemic aspirin provocation test (ATA-1, n = 83) and outpatients randomly selected from a large-scale dataset (ATA-2, n = 914), as well as a healthy control group (HC, n = 2313)., Results: At the age of asthma onset, there was a low frequency of current smokers (9.7%), but a high frequency of past smokers (20.2%) in the AERD group compared with the ATA-1 (20.5% and 12.0% for current and past smokers, respectively), ATA-2 (24.5% and 10.3%, respectively), and HC group (26.2% and 12.6%, respectively). After adjustment for confounding variables, AERD was positively associated with smoking cessation between 1 and 4 years before disease onset compared with the ATA-2 group (adjusted odds ratio [aOR] 4.63, 95% confidence interval [CI]: 2.16-9.93) and the HC group (aOR 4.09, 95% CI: 2.07-8.05), implying that smoking cessation was followed by the development of AERD., Conclusion: Smoking cessation may be a risk factor for the development of AERD., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To clarify the differences between postmortem CT (PMCT) and autopsy findings in the postmortem detection of cervical spine injuries (CSIs)., Materials and Methods: Our department's forensic pathology database was searched for CSI cases. In each case, the autopsy data and radiologists' interpretations were reviewed for the presence of bone fractures and intervertebral injuries., Results: The study included 42 cases. For both bone fractures and intervertebral injuries, no substantial concordance between PMCT and autopsy findings was observed (McNemar's test: p<0.001 and p<0.001, respectively). Regarding bone fractures, more injuries were detected with CT than with autopsy (CT: 74, autopsy: 23). The percentage of CT-detected fractures that were missed at autopsy (77.0%, 57/74) was higher than the percentage of autopsy-detected fractures missed with CT (26.1%, 6/23). Regarding intervertebral injuries, fewer injuries were detected with CT than with autopsy (CT: 40, autopsy: 80). The percentage of CT-detected injuries that were missed at autopsy (35.0%, 14/40) was lower than the percentage of autopsy-detected injuries that were missed with CT (67.5%, 54/80)., Conclusions: A substantial number of CSIs were detected by either PMCT or autopsy alone. Accurate evaluation for CSI requires the use of both methods., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: To assess the efficacy of screening with concurrent liquid-based cytology and human papillomavirus (HPV) testing for primary cervical cancer screening, we initiated a randomized trial entitled CervIcal cancer screening Trial by Randomization of HPV testing intervention for Upcoming Screening (CITRUS)., Methods: Between June 2013 and March 2015, women aged 30-64 years of age who participated in a regular cervical cancer screening program (every 2 years) were invited to enrollment of our study. After giving their informed consent, 18,402 women were randomly assigned to liquid-based cytology as the control group (n=9145) or to HPV DNA testing with liquid-based cytology as the intervention group (n=9257). We subsequently compared the incidence rate of cervical intraepithelial neoplasia (CIN), the rate of false positive tests and the rate of overdiagnosis, as well as assessing the risks and benefits of receiving screening for women in both groups. The primary outcome of our study was the incidence of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) during the study period of around 6 years., Results: In the control group, 97.9% of women were NILM, and 2.06% ASC-US or worse (ASC-US+). In the intervention group, 87.13% of women were NILM/HPV negative, 0.72% ASC-US/HPV negative, 10.34% NILM/HPV positive, 0.69% ASC-US/HPV positive, 0.90% worse than ASC-US/either HPV. Positive HPV testing was not linearly related to age in our study., Conclusions: Insights from CITRUS will provide future prospects for cervical cancer screening focused on the use of HPV testing in Japan., Clinical Trial Registration Number: NCT01895517, UMIN000010843, TRIUC1312., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aims: The purpose of this study was to identify determinants of sudden death among clinical information in combination with cardiac fatty acid metabolism for better risk-stratification of haemodialysis patients., Methods and Results: Clinical and imaging data from 677 haemodialysis patients enrolled in the beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP) SPECT Analysis for Decreasing Cardiac Events in Hemodialysis Patients (B-SAFE) study were analysed in this study. During a 3-year prospective follow-up interval, 20 sudden deaths were observed. Compared with non-sudden death patients, sudden death patients more frequently had an increased C-reactive protein level (>2.38 mg/dL), electrocardiographic abnormal Q-wave and increased BMIPP abnormality score (>16). Patients with BMIPP score >16 and at least one of the other predictors had significantly lower event-free rates than did those without the BMIPP abnormality (P < 0.001). Univariate and multivariate Cox regression analyses revealed increased C-reactive protein level, abnormal Q-wave, and greater BMIPP abnormality as significant sudden death predictors with hazards ratios of 6.83 (95% CI: 1.76-26.47, P = 0.005), 17.73 (95% CI: 4.91-63.98, P < 0.001), and 10.58 (95% CI; 3.84-29.14, P < 0.001), respectively. The addition of BMIPP score >16 to the other clinical predictors increased the hazard ratio and receiver-operating characteristic analysis-area under the curve up to 145.22 (95% CI; 0.34-695.09) and to 0.677-0.690, respectively., Conclusions: Increased C-reactive protein, electrocardiographic Q-wave, and impaired myocardial fatty acid metabolism are independently and synergistically related to sudden death risk in haemodialysis patients. The non-invasive strategy presented here might contribute to the identification of haemodialysis patients who can most benefit from a prophylactic treatment against sudden death., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

The incidence of second primary malignancies (SPMs) in Japanese patients with myeloma or myeloma-related diseases was studied by using the Kansai Myeloma Forum (KMF) database registered from November 2012 to March 2015. We studied 1,571 cases. Hematologic malignancies were documented in 10 patients, and solid tumors in 36 during this period. The cumulative 5-year incidence was estimated to be 1.0% for hematological malignancies and 3.7% for solid tumors. In the patients with smoldering myeloma or MGUS without treatment, solid tumors but not hematologic malignancies developed, though the cumulative incidence of each malignancy did not differ significantly from that in patients receiving treatment. Although statistical analysis showed that treatment with melphalan, bortezomib, lenalidomide, or thalidomide had no effect on the occurrence of hematological malignancies, lenalidomide administration was more frequent in the patients with solid tumors. To evaluate the SPMs in myeloma or myeloma-related diseases more accurately, accumulation of a larger number of patients and longer observation are needed.

The phase I/II study of melphalan-prednisolone-bortezomib (MPB) therapy in Japanese patients with previously untreated multiple myeloma (MM) who are ineligible for hematopoietic stem cell transplantation (JPN-102 trial) (registered between July 2008 and March 2011) showed an overall response rate in the MPB arm equivalent to that of the VISTA trial. In this study, we followed up the clinical data of 92 of the 101 patients registered in the JPN-102 trial to clarify the long-term outcomes of MPB therapy. The median follow-up period was 50.8 (0.9-66.1) months. The median age of this cohort was 72 (48-84) years. The median progression-free survival was 25.7 (95%CI: 21.3-33.9) months and the overall survival rates at 1, 3 and 5 years were 98, 86 and 76%, respectively. There was no significant difference in either progression-free survival or overall survival when comparing a total bortezomib amount of 39 mg/m 2 or more being administered versus less than 39 mg/m 2 . The outcomes of the JPN-102 cohort appeared, at a minimum, to not be inferior to those of the MPB cohort in the VISTA trial. A prospective trial is needed to establish the MPB regimen as being suitable for Japanese patients with multiple myeloma.

Objective: The purpose of this study was to assess the incidence of spinal cord injuries without radiographic abnormalities (SCIWORA) on postmortem MDCT studies and to characterize this entity in detail., Materials and Methods: Data from consecutive autopsies from October 2009 through December 2012 were searched, yielding 30 cases of cervical spinal cord injuries. Two board-certified radiologists interpreted postmortem MDCT images acquired before autopsy. Cases with normal findings were defined as SCIWORA., Results: Postmortem MDCT images in 6 of 30 cases (20%; 95% CI, 8-39%) met SCIWORA criteria. In all these cases, traumatic death was not apparent before CT, the highest injury level was below C3, and fractures were not identified at autopsy. All subjects had occult disk injuries and perivertebral hemorrhage. Potentially fatal CT-detectable injuries to other parts of the body were not seen in five of six SCIWORA cases., Conclusion: A substantial proportion of fatal spinal cord injuries are without radiographic abnormalities at CT. Forensic radiologists and other interpreters of postmortem MDCT images must be aware of this entity to avoid excluding spinal cord injuries solely on the basis of postmortem MDCT findings. Special care is necessary in cases of unknown circumstances of death without abnormal CT findings. MRI may be used for further examination in the future, but until then, MDCT cannot replace autopsy for detecting SCIWORA.