Search

Aim: The influence of family history of diabetes, probably reflecting genetic and lifestyle factors, on the association of combined genetic and lifestyle risks with diabetes is unknown. We examined these associations., Methods: This cross-sectional study included 9,681 participants in the Tohoku Medical Megabank Community-based Cohort Study. A lifestyle score, which was categorized into ideal, intermediate, and poor lifestyles, was given. Family history was obtained through a self-reported questionnaire. A polygenic risk score (PRS) was constructed in the target data (n=1,936) using publicly available genome-wide association study summary statistics from BioBank Japan. For test data (n=7,745), we evaluated PRS performance and examined the associations of combined family history and genetic and lifestyle risks with diabetes. Diabetes was defined as non-fasting blood glucose ≥ 200 mmHg, HbA1c ≥ 6.5%, and/or self-reported diabetes treatment., Results: In test data, 467 (6.0%) participants had diabetes. Compared with a low genetic risk and an ideal lifestyle without a family history, the odds ratio (OR) was 3.73 (95% confidence interval [CI], 1.92-7.00) for a lower genetic risk and a poor lifestyle without a family history. Family history was significantly associated with diabetes (OR, 3.58 [95% CI, 1.73-6.98]), even in those with a low genetic risk and an ideal lifestyle. Even among participants who had an ideal lifestyle without a family history, a high genetic risk was associated with diabetes (OR, 2.49 [95% CI, 1.65-3.85]). Adding PRS to family history and conventional lifestyle risk factors improved the prediction ability for diabetes., Conclusions: Our findings support the notion that a healthy lifestyle is important to prevent diabetes regardless of genetic risk.

Background: It has been pointed out that eye-level greenery streetscape promotes leisure walking which is known to be a health -positive physical activity. Most previous studies have focused on the total amount of greenery in the eye-level streetscape to investigate its association with walking behaviour. While it is acknowledged that taller trees contribute to greener environments, providing enhanced physical and psychological comfort compared to lawns and shrubs, the examination of streetscape metrics specifically focused on greenery height remains largely unexplored. Therefore, this study examined the relationship between objective indicators of street greenery categorized by height from a pedestrian viewpoint and leisure walking time., Methods: We created streetscape indices of street greenery using Google Street View Images at 50-m intervals in an urban area in Sendai City, Japan. The indices were classified into four ranges according to the latitude of the virtual hemisphere centred on the viewer. We then investigated their relationship to self-reported leisure walking., Results: Positive associations were identified between the street greenery in higher positions and leisure walking time, while there was no significant association between the greenery in lower positions., Conclusion: The findings indicated that streets with rich greenery in high positions may promote residents' leisure walking, indicating that greenery in higher positions contributes to thermally comfortable and aesthetic streetscapes, thus promoting leisure walking. Increasing the amount of greenery in higher positions may encourage residents to increase the time spent leisure walking., (© 2023. The Author(s).)

Background: Several studies have reported that a switch to the dopamine partial agonist (DPA) aripiprazole (ARP), especially when the switch is abrupt, is likely to fail and sometimes worsen psychosis in schizophrenia patients already under high-dose antipsychotic treatment. Such a switching failure is speculated to be related to be the dopamine supersensitivity state. The risks of switching to the DPA brexpiprazole (BREX) have not been reported., Aims and Methods: We retrospectively analyzed the cases of 106 patients with schizophrenia to identify any factors related to the success or failure of switching to BREX., Results: The comparison between the patients with dopamine supersensitivity psychosis ( n  = 44) and those without ( n  = 62) revealed no significant difference in the switching failure judged at the sixth week. A comparison of the patients with successful switching ( n  = 80) and those who failed ( n  = 26) revealed that patients with treatment-resistant schizophrenia (TRS) were significantly more likely to fail. A logistic regression analysis also revealed that patients with past failure of switching to ARP are likely to succeed in switching to BREX. The 2-year follow-up of the patients with successful switching to BREX suggested that the patients who were treated with BREX, even temporarily, experienced some improvement in their Global Assessment of Functioning and Clinical Global Impression-Severity scores., Conclusions: Overall, the results indicate that patients with schizophrenia can be switched more safely to BREX compared to ARP. However, the failure of switching to BREX could be higher in patients with TRS, and thus, starting BREX treatment in refractory patients warrants careful monitoring., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: NK reports honoraria from Otsuka Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd., Janssen Pharmaceutical K.K., Meiji Seika Pharma Co., Ltd., Mitsubishi Tanabe Pharma Co., Ltd., Yoshitomi Pharmaceutical Industries, Ltd., and Eisai Co. Ltd. YN reports honoraria from Otsuka Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd., Meiji Seika Pharma Co., Ltd., and Takeda Pharmaceutical Co., Ltd. TsuS reports grant from Shionogi & Co., Ltd. and honoraria from Sumitomo Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Ltd., Nobelpharma Co., Ltd., Kyowa Kirin Co., Ltd., Towaseiyaku Co., Ltd., Eisai Co. Ltd., Janssen Pharmaceutical K.K., Yoshitomi Pharmaceutical Industries, Ltd., and Shionogi & Co., Ltd. HK reports honoraria from Otsuka Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd., Janssen Pharmaceutical K.K., and Meiji Seika Pharma Co., Ltd. MI received consultant fees from Eli Lilly Japan K.K., Sumitomo Pharma Co., Ltd., Pfizer Japan Inc., Abbott Japan Co., Ltd. and Janssen Pharmaceutical K.K., and reports honoraria from Janssen Pharmaceutical K.K., Eli Lilly Japan K.K., Otsuka Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Ltd., Astellas Pharma Inc., Sumitomo Pharma Co., Ltd., Ono Pharmaceutical Co., Ltd., GlaxoSmithKline K.K., Takeda Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., MSD K.K., Eisai Co. Ltd., Daiichi-Sankyo Co. Ltd., Novartis Pharma K.K., Teijin Ltd., Shionogi & Co., Ltd., Hisamitsu Pharmaceutical Co., Inc. and Asahi Kasei Corporation. FY, SK, YY, TakS TO, MK, TY has no conflict of interest to declare.

Aim: We examined the association between the carotid intima medica thickness (cIMT) and risk factors for atherosclerosis based on the Japan Atherosclerosis Society 2022 Atherosclerosis Prevention Guideline., Methods: Using data from the Tohoku Medical Megabank Community-based Cohort Study, we performed a cross-sectional study that enrolled 13,366 participants (age ≥ 20 years) with an analysis of covariance to assess associations between cIMT and risk factors for atherosclerosis. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. Analysis was conducted in the model adjusted for age, sex, smoking status, drinking status, body mass index (BMI), systolic blood pressure (SBP), glycated hemoglobin (HbA1c), high-density lipoprotein-cholesterol (HDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C), and height., Results: In this study cohort, the average age and cIMT were 57.3 (13.8) years and 0.61 (0.13) mm, respectively, which included 3,988 males (29.8%). Males had a higher cIMT than did the females. Age, height, BMI, SBP, HbA1c, and non-HDL-C were positively associated with cIMT. HDL-C was inversely associated with cIMT. Compared with never drinkers, current drinkers (≥ 46.0 g/day) had a significantly decreased cIMT., Conclusions: The cIMT was associated with atherosclerosis risk factors including age, sex, BMI, SBP, HbA1c, non-HDL-C, and HDL-C, and adequate control of risks in high-risk individuals might be required to prevent atherosclerotic cardiovascular diseases.

Background: Birth weight, as a measure of intrauterine growth, is commonly used in epidemiological studies and is reported to be associated with adult lung function. However, findings regarding this association in previous studies have been inconsistent. Furthermore, no studies have reported associations stratified by age or smoking status, or adjusted for eosinophil count or other parameters related to type 2 airway inflammation., Methods: This cross-sectional study included 2632 men and 7237 women aged ≥20 years living in Miyagi Prefecture, Japan. Lung function was assessed based on spirometry. Birth weight data were obtained through a questionnaire survey. Analysis of covariance was used to evaluate the associations between birth weight and lung function, adjusting for potential confounders. Stratified analyses by age and smoking status were also conducted, together with a sub-analysis for low birth-weight participants., Results: Birth weight was positively associated with forced expiratory volume in 1 s (FEV 1 ) for both sexes and with vital capacity in women, after adjusting for height, age, smoking status, and parameters related to type 2 airway inflammation. The stratified analysis for smoking status revealed associations in never-smokers and ex-smokers. When stratified by age, the associations were confirmed in middle-aged participants. The effect of smoking status on the FEV 1 of low birth-weight participants was not significant., Conclusions: Our analysis of a large, Japanese adult population showed that birth weight was independently and positively associated with adult lung function, even after adjustment for age, height, smoking status, and parameters related to type 2 airway inflammation., Competing Interests: Conflict of Interest The authors have no conflicts of interest., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Aim: Impaired lung function is associated with atherosclerotic vascular events. Carotid intima-media thickness (cIMT) is a marker for subclinical atherosclerosis. However, few studies have examined the association between lung function and cIMT among never smokers or individuals stratified by age. We investigated the association between lung function and cIMT in the Japanese population., Methods: We conducted a cross-sectional study of 3,716 men and 8,765 women aged 20 years or older living in Miyagi Prefecture, Japan. Lung function was evaluated using forced expiratory volume at 1 s (FEV 1 ) and forced vital capacity (FVC) was measured using spirometry. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. An analysis of covariance was used to assess associations between lung function and cIMT and adjusted for potential confounders. A linear trend test was conducted by scoring the categories from 1 (lowest) to 4 (highest) and entering the score as a continuous term in the regression model., Results: After adjusting for potential confounders including passive smoking, lower FEV 1 and FVC were associated with higher cIMT in both men and women (P＜0.001 for linear trend). This association was confirmed even when we restricted our study to never smokers. Furthermore, even when we stratified by age, an inverse association between lung function and cIMT was confirmed in middle-aged (40-64 years) and elderly participants (65-74 years)., Conclusions: Lower lung function was associated with higher cIMT in the Japanese population independent of age and smoking. Assessment of atherosclerosis or lung function may be required for individuals with lower lung function or atherosclerosis.

Impaired % predicted value forced vital capacity (% FVC) is related to higher all-cause mortality in aged adults, and strong muscle force may improve this relationship. A muscle disease, sarcopenia, causes higher mortality. We aimed to identify the unknown disease that relates impaired % FVC with higher mortality in aged adults among the three major leading causes of death, and the effect of strong leg force on this relationship. Cox proportional hazard model analyzed the longitudinal Tsurugaya cohort that registered 1048 aged Japanese for 11 years. The primary outcome was the relationship between % FVC and mortality by cancer, cardiovascular disease, or pneumonia. Exposure variables were % FVC or leg force divided by 80% or median values, respectively. The secondary outcome was the effects of leg force on the relationship. Among the diseases, % FVC < 80% was related only to higher pneumonia mortality (hazard ratio [HR], 4.09; 95% CI, 1.90-8.83) relative to the % FVC ≥ 80% group before adjustment. Adding the leg force as an explanatory variable reduced the HR to 3.34 (1.54-7.25). Weak leg force might indicate sarcopenia, and its prevention may improve higher pneumonia mortality risk related to impaired % FVC, which we may advise people in clinical settings.

People who experience natural disasters have a high risk of developing cardiovascular diseases. We investigated the association between the extent of house collapse and urine sodium-to-potassium (UNa/K) ratio of 2011 Great East Japan Earthquake victims. We used the baseline survey data of the Tohoku Medical Megabank Project Community-Based Cohort Study of 29 542 individuals (aged 20-74 years) residing in the affected areas. The UNa/K ratio was calculated using spot urinary electrolyte values. Analysis of covariance was used to calculate the multivariate-adjusted geometric means of the UNa/K ratio in the following groups stratified according to the self-reported extent of house collapse: total collapse (TC), half collapse (HC), partial collapse (PC), and no damage (ND). Multivariable-adjusted odds ratios (ORs) for a high UNa/K ratio were calculated using logistic regression. The TC, HC, PC, and ND groups comprised 5 359 (18.1%), 3 576 (12.1%), 7 331 (24.8%), and 13 276 (44.9%) participants, respectively. The TC (3.33; 95% confidence interval [CI], 3.28-3.38), HC (3.37; 3.30-3.43), and PC (3.32; 3.28-3.37) groups had significantly higher multivariate-adjusted geometric means of the UNa/K ratio than the ND (3.24; 3.21-3.27) group. The multivariable-adjusted ORs (95% CIs) for a high UNa/K ratio in the TC, HC, and PC groups vs. the ND group were 1.07 (0.99-1.15), 1.20 (1.11-1.31), and 1.20 (1.12-1.28), respectively. Similar associations between house collapse and UNa/K ratio were observed for both sexes. We report that victims of a natural disaster tend to have a diet with high sodium-to-potassium ratio., (© 2023. The Author(s).)

White blood cell (WBC) count profiles in anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are still unknown. This study evaluated the total WBC count, differential WBC counts, monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) in patients with these diseases within three months from an attack before acute treatment or relapse prevention and compared the profiles with those in matched volunteers or in multiple sclerosis (MS) patients. AQP4-NMOSD patients (n = 13) had a higher neutrophil count (p = 0.0247), monocyte count (p = 0.0359), MLR (p = 0.0004), and NLR (p = 0.0037) and lower eosinophil (p = 0.0111) and basophil (p = 0.0283) counts than those of AQP4-NMOSD-matched volunteers (n = 65). Moreover, patients with MOGAD (n = 26) had a higher overall WBC count (p = 0.0001), neutrophil count (p < 0.0001), monocyte count (p = 0.0191), MLR (p = 0.0320), and NLR (p = 0.0002) than those of MOGAD-matched volunteers (n = 130). The three demyelinating diseases showed similar levels of the total and differential WBC counts; however, MOGAD and MS showed different structures in the hierarchical clustering and distributions on a two-dimensional canonical plot using differential WBC counts from the other three groups. WBC count profiles were similar in patients with MOGAD and MS but differed from profiles in matched volunteers or patients with AQP4-NMOSD., (© 2023. The Author(s).)

Background: Although several studies have shown an inverse association between lung function and hypertension, few studies have examined the association between lung function and hypertension among never-smokers, and no study has investigated the association between lung function and home hypertension. We investigated the associations between lung function and hypertension in a Japanese population., Individuals and Methods: We conducted a cross-sectional study of 3728 men and 8795 women aged 20 years or older living in Miyagi Prefecture, Japan. Lung function was assessed using forced expiratory volume at 1 s (FEV 1 ) and forced vital capacity (FVC), measured by spirometry. Hypertension was defined as a casual blood pressure at least 140/90 mmHg and/or self-reported treatment for hypertension. Home hypertension was defined as morning home blood pressure at least 135/85 mmHg and/or self-reported treatment for hypertension. Multivariate logistic regression models adjusted for potential confounders were used to assess the association between lung function and hypertension., Results: The mean ages (±SD) of men and women were 60.1 (±14.0) years and 56.2 (±13.4) years, respectively, and 1994 (53.5%) men and 2992 (34.0%) women had hypertension. In the multivariable models, FEV 1 and FVC were inversely associated with hypertension. Inverse associations between lung function and hypertension were observed even among never-smokers. Furthermore, reduced lung function was associated with higher prevalence of home hypertension in men and women., Conclusion: Reduced lung function was associated with higher prevalence of hypertension, independent of smoking status. Assessment of the lung function or blood pressure may be required in individuals with reduced lung function or hypertension., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: Although many epidemiological studies have shown that obesity assessed by body mass index is associated with carotid intima-media thickness (cIMT), few studies have evaluated fat-free mass, which is a component of body composition. We investigated the associations between the combined fat mass index (FMI) and fat-free mass index (FFMI) with cIMT., Methods: We conducted a cross-sectional study of 3,873 men and 9,112 women aged 20 years or older who lived in Miyagi prefecture, Japan. The FMI and FFMI were calculated as fat mass and fat-free mass divided by height squared, respectively. The indices were classified into sex-specific quartiles and were combined into 16 groups. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. An analysis of covariance was used to assess associations between the combined FMI and FFMI with cIMT adjusted for age and smoking status. The linear trend test was conducted by stratifying the FMI and FFMI, scoring the categories from 1 (lowest) to 4 (highest), and entering the number as a continuous term in the regression model., Results: In multivariable models, a higher FMI was not related to higher cIMT in men and women in most FFMI subgroups. Conversely, a higher FFMI was related to higher cIMT in all FMI subgroups (p＜0.001 for linear trend)., Conclusions: FMI was not associated with cIMT in most FFMI subgroups. Conversely, FFMI was positively associated with cIMT independently of FMI.

Both the underutilization of clozapine and treatment resistance of patients to clozapine are serious problems worldwide. Identifying clinical markers predicting response to clozapine would help clinicians more effectively utilize clozapine treatment. The present study retrospectively assessed dopamine supersensitivity psychosis (DSP) in addition to other measures such as age at disease onset and delay of clozapine introduction for a total of 47 treatment-resistant schizophrenia (TRS) patients. The response to clozapine was judged with CGI-C at 1 and 2 years from clozapine introduction. Results revealed that the DSP group tended to have a longer delay between designation of TRS and introduction of clozapine and continued to have slightly more severe psychopathology after treatment with clozapine, showing only slight improvement. The logistic regression analysis showed that the age at disease onset was the only significant indicator, predicting responsiveness to clozapine: patients with an onset age <20 years had a significantly better response to clozapine than patients with an onset age ≥20 years. The present study suggests that DSP might be related to a longer delay in clozapine introduction and the persistence of refractory symptoms despite clozapine treatment, whereas early age of disease onset might be related to a better response to clozapine., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives Neoadjuvant therapy followed by radical resection improves the borderline-resectable pancreatic cancer (BRPC) prognosis; however, the optimal therapeutic regimen remains unclear. Gemcitabine plus nab-paclitaxel (GnP) showed a high anti-tumor effect in primary lesions in a prospective study for metastatic disease. However, evidence concerning its feasibility is still lacking in patients with BRPC. We therefore evaluated the tolerability of neoadjuvant GnP (NAC-GnP) for BRPC. Methods This single-center prospective study evaluated 10 patients with BRPC who were treated with two cycles of NAC-GnP. The primary endpoint was feasibility for NAC-GnP. Treatment feasibility was defined as a successful outcome in at least eight patients. Results Ten patients who had BRPC in contact with the celiac artery (n=5), superior mesenteric artery (n=3), or hepatic artery (n=2) were enrolled. The median age was 75 (range, 40-82) years old. Grade 3 anorexia and grade 2 pneumonia occurred in one patient each, so treatment was feasible in eight patients. The median primary tumor reduction and response rates were 33% (range, 0-68%) and 60%, respectively. Six of eight patients who had abnormal CA19-9 levels at the time of enrolment showed a decrease in CA19-9 levels, with a median decrease of 72%. Five patients underwent radical resection, including R0 resection in four. Postoperative grade IIIa Clavien-Dindo complications occurred in one patient (upper gastrointestinal bleeding and pancreatic fistula). Conclusion Two-cycle NAC-GnP is a feasible treatment for patients with BRPC. Further studies on NAC-GnP in patients with BRPC are warranted.

The Tohoku Medical Megabank Project (TMM) has been conducting a birth and three-generation cohort study (the BirThree Cohort Study). We recruited 73,529 pregnant women and their family members for this cohort study, which included 23,143 newborns and 9,459 of their siblings. We designed and are in the process of conducting three-step health assessments for each newborn at approximately ages of 5, 10 and 16. These health assessments are administered at seven community support centers. Trained genome medical research coordinators conduct physical examinations of and collect biological specimens from each participant. The Sendai Children's Health Square has been established as the headquarters for these child health assessments and is utilized to accumulate knowledge that can facilitate the proper practice of child health assessments. We designed all the relevant health assessments facilities to allow parents and their children to participate in the health assessments concomitantly. Our centers serve as places where child participants and their parents can feel at ease as a result of the implementation of safety measures and child hospitality measures. The TMM BirThree Cohort Study is in the process of conducting strategically detailed health assessments and genome analysis, which can facilitate studies concerning the gene-environment interactions relevant to noncommunicable diseases. Through these operations, our study allows for a significant depth of data to be collected in terms of the number of biospecimens under study and the comprehensiveness of both basic and clinical data alongside relevant family information.

Background: Olfactory function decline has recently been reported to be associated with a risk of cognitive impairment. Few population-based studies have included younger adults when examining the association between olfactory test data with multiple odor intensities and suspected cognitive impairment., Objective: We investigated the association between high-resolution olfactory test data with fewer odors and suspected cognitive impairments. We also examined the differences between older and younger adults in this association., Methods: The Japanese version of the Montreal Cognitive Assessment (MoCA-J) was administered to 1,450 participants, with three odor-intensity-level olfactometry using six different odors. Logistic regressions to discriminate suspected cognitive impairment were conducted to examine the association, adjusted for age, sex, education duration, and smoking history. Data were collected from the Program by Tohoku University Tohoku Medical Megabank Organization, with an additional olfactory test conducted between 2019 and 2021., Results: We generally observed that the lower the limit of distinguishable odor intensity was, the higher the MoCA-J score was. The combination of spearmint and stuffy socks contributed most to the distinction between suspected and unsuspected cognitive impairment. Furthermore, the association was significant in women aged 60-74 years (adjusted odds ratio 0.881, 95% confidence interval [0.790, 0.983], p = 0.024)., Conclusions: The results indicate an association between the limit of distinguishable odor intensity and cognitive function. The olfactory test with multiple odor intensity levels using fewer odors may be applicable for the early detection of mild cognitive impairment, especially in older women aged 60-74 years.

Cell-based therapies hold great promise for the treatment of peripheral arterial disease (PAD), especially in patients presenting with severe limb ischemia, although the optimal strategy remains to be explored. In this study, we evaluated the therapeutic effect of intravenous administration of human Muse cells, a unique subpopulation of mesenchymal stem cells (MSC), using a mouse model of hindlimb ischemia (HLI) without an immunosuppressant. Compared with the phosphate buffered saline (PBS) or non-Muse MSC groups, the Muse group showed significantly higher laser doppler blood flow in the ischemic limb at days 7 and 14 after HLI. Increased microvascular density [percent area of CD31(+) cells] and reduced interstitial fibrosis in the ischemic limb muscle were also observed in the Muse group. mCherry-expressing Muse cells were found in the ischemic border zone and expressed CD31 but did not in the non-ischemic limb. Muse cells produced higher amounts of vascular endothelial growth factor (VEGF) than non-Muse cells under normoxic and hypoxic conditions in vitro . In the ischemic muscle, tissue VEGF concentration and angiogenesis-related genes such as Vegfa , Angpt1 , Pdgfb , and Igf1 were significantly higher in the Muse group than in the other two groups. In addition, the proportion of M2 macrophages to total macrophages and the ratio of anti-inflammatory-related genes such as IL-10 , Arg1 , and CD206 per iNOS were significantly higher in the Muse group than in the other two groups. In summary, Muse cells exert pleiotropic effects in a mouse model of HLI, and therefore may provide a novel therapeutic approach for the treatment of PAD patients with severe limb ischemia., Competing Interests: Authors YK and MD are parties to a joint research agreement for industrial applications of Muse cells with Life Science Institute, Inc. (LSII: Tokyo, Japan). Authors TKi and SM received a joint research fee from LSII for critical limb ischemia. Author MD holds a patent for Muse cells and the isolation method for Muse cells which are exclusive licensed to LSII. Authors MD and SM hold a patent for the application of Muse cells in the treatment of critical limb ischemia. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hori, Kitani, Yanishi, Suga, Kogure, Kusaba, Kushida, Dezawa and Matoba.)

Background: Previous observational studies have shown similarities in cardiometabolic risk factors between spouses. It is still possible that this result reflects the age similarity of spouses rather than environmental factors of spouses (e.g. cohabitation effect). To clarify the importance of mate cardiometabolic risk factors for similarity of environmental factors, it is necessary to examine whether they are observed in random male-female pairs while maintaining the age of the spousal pairs. This study aimed to determine whether the similarities found between spousal pairs for cardiometabolic risks were also observed between random male-female pairs., Methods: This cross-sectional study included 5,391 spouse pairs from Japan; data were obtained from a large biobank study. For pairings, women of the same age were randomly shuffled to create new male-female pairs of the same age as that of the original spouse pairs. Similarities in cardiometabolic risk factors between the random male-female pairs were analysed using Pearson's correlation or age-adjusted logistic regression analyses., Results: The mean ages of the men and women were 63.2 and 60.4 years, respectively. Almost all cardiometabolic risk factors similarities were not noted in cardiometabolic risk factors, including the continuous risk factors (anthropometric traits, blood pressure, glycated haemoglobin level, and lipid traits); lifestyle habits (smoking, drinking, and physical activity); or diseases (hypertension, type 2 diabetes mellitus, and metabolic syndrome) between the random male-female pairs. The age-adjusted correlation coefficients ranged from - 0.007 for body mass index to 0.071 for total cholesterol. The age-adjusted odds ratio (95% confidence interval) for current drinkers was 0.94 (0.81 - 1.09); hypertension, 1.07 (0.93 - 1.23); and type 2 diabetes mellitus, 1.08 (0.77 - 1.50)., Conclusion: In this study, few similarities in cardiometabolic risk factors were noted among the random male-female pairs. As spouse pairs may share environmental factors, intervention strategies targeting lifestyle habits and preventing lifestyle-related diseases may be effective., (© 2022. The Author(s).)

Competing Interests: Naohiro Okano has received honoraria from Taiho Pharmaceutical, Eli Lilly Japan, Chugai Pharma, and Ono Pharmaceutical. Other authors declare no conflicts of interest associated with this manuscript.

Development of methods for population screening is necessary to improve the efficiency of secondary prevention of diseases. Until now, a common cutoff has been used for all people in the data set. However, if big data for health information can be used to modify individual cutoffs according to background factors, it may avoid wasting medical resources. Here we show that the estimated prevalence of the Center for Epidemiologic Studies Depression Scale positivity can be visualized by a heatmap using background factors from epidemiological big data and scores from the Athens Insomnia Scale. We also show that cutoffs based on the estimated prevalence can be used to decrease the number of people screened without decreasing the number of prevalent cases detected. Since this method can be applied to the screening of different outcomes, we believe our work can contribute to the development of efficient screening methods for various diseases., (© 2022. The Author(s).)

Objective: This study aims to evaluate the long-term impact of living in postdisaster prefabricated temporary housing on social interaction activities and mental health status., Methods: A total of 917 adult residents in a coastal town, whose residences were destroyed by the tsunami caused by the Great East Japan Earthquake (GEJE), were enrolled for the assessment held 5 y after the disaster. They answered questions about their experience and consequence of living in prefabricated temporary housing after the disaster. Their present scores on 5 types of self-reported measures regarding the psychosocial or psychiatric status and their present and recalled social interaction activities were cross-sectionally collected., Results: A total of 587 (64.0%) participants had a history of living in prefabricated temporary housing, while the other 330 (36.0%) had not. The prevalence of social interaction activities significantly decreased after the GEJE. However, the experience of living in prefabricated temporary housing did not adversely affect the subsequent social interaction activities or mental conditions of the participants 5 y after the disaster., Conclusions: Living in postdisaster prefabricated temporary housing may not negatively impact subsequent psychosocial conditions or social interaction activities 5 y later.

Pancreatic cancer has the poorest prognosis among digestive cancers. During the 1990s, the 5-year survival rate of surgical patients with pancreatic cancer was 14% in Japan. However, survival rates have increased to 40% in the 2020s due to the refinement of surgical procedures and the introduction of perioperative chemotherapy. Several pivotal randomized controlled trials have played an indispensable role to establish each standard treatment strategy. Resectability of pancreatic cancer can be classified into resectable, borderline resectable, and unresectable based on the anatomic configuration, and multidisciplinary treatment strategies for each classification have been revised rapidly. Investigation of superior perioperative adjuvant treatments for resectable and borderline resectable pancreatic cancer and the establishment of optimal conversion surgery for unresectable pancreatic cancer are the progressive subjects.

Background: Dopamine supersensitivity psychosis (DSP) is an unstable psychotic state in patients with schizophrenia due to an upregulation of dopamine D2 receptors induced by antipsychotic medication. Long-acting antipsychotic injectable (LAI) could be advantageous for controlling the dopamine supersensitivity state, but it is not known if long-term treatment with LAI might ultimately lead to development or exacerbation of DSP., Methods: The present study included 58 patients who had been treated with LAI for at least 3 years, with medical records for the 3 years before its introduction. Those records were used to classify patients as having DSP (n = 30, DSP group) or not (n = 28, non-DSP group). The effects of LAI treatments on the clinical course during the 3 years after the LAI introduction were compared between the 2 groups., Results: Both groups demonstrated significant decreases in antipsychotic dosage (combined LAI and oral antipsychotics) and a significant improvement measured by clinical global impression-improvement. These indicators did not differ between them, suggesting similar efficacy of LAI for both groups. On average, the DSP group was treated with a higher dose of antipsychotics (1004.8 mg) before the LAI introduction compared with the non-DSP group but reduced them to within the standard dose range (662.0 mg) after the introduction of LAI., Conclusions: Our results indicated the effectiveness of LAI treatment for at least 3 years for patients with DSP, suggesting that this treatment strategy is unlikely to worsen DSP. The efficacy might be explained by the large decrease in the total antipsychotic dose with the introduction of LAI., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The aim of this study was to search for routine blood test biomarkers in patients with physical symptoms but without a diagnosis after comprehensive routine screening diagnostic examinations., Methods: A total of 228 adults aged < 65 years who presented with physical complaints without known causes after comprehensive screening diagnostic examinations and 228 age- and sex-matched healthy controls without physical complaints were enrolled. The blood cell count data at the first hospital visit were compared between these groups., Results: Total white blood cell ( p  = 0.2143), red blood cell ( p  = 0.8954), and platelet ( p  = 0.7716) counts did not differ between the groups. The monocyte count ( p  = 0.0014) and resultant monocyte-to-lymphocyte ratio ( p  < 0.0001) were higher in the symptomatic group, while the other white blood cell subtypes did not differ significantly between the two groups. In the symptomatic group, patients with a monocyte-to-lymphocyte ratio > 0.25 were likely to have unexplained nonfocal physical symptoms ( p  < 0.0001). The characteristic findings included fatigability ( p  < 0.0001), prolonged slight fever ( p  = 0.0005), and widespread pain ( p  < 0.0001). The monocyte-to-lymphocyte ratio level was correlated with the proportion of patients with unexplained nonfocal symptoms., Conclusion: The blood cell count profile was largely the same between healthy individuals and patients with unexplained physical symptoms. However, patients with unexplained nonfocal physical complaints were likely to show an elevated monocyte-to-lymphocyte ratio, typically > 0.25., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) are enzymes associated with diabetes mellitus (DM) prevalence. However, limited information is available regarding the association of liver enzymes and DM consistently present in obese and non-obese individuals. We examined whether the combination of ALT and GGT enzymes is associated with the prevalence of DM, regardless of obesity, in a general Japanese population., Methods: We conducted a cross-sectional study of 62,786 participants aged ≥20 years who lived in Miyagi and Iwate, Japan. We divided all the participants into eight groups according to the ALT level (low: <30 IU/L and high: ≥30 IU/L), GGT level (low: <50 IU/L and high: ≥50 IU/L), and the presence of obesity. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression analysis, adjusting for potential confounders, to determine associations of the combination of ALT and GGT levels and obesity with DM prevalence., Results: Overall, 6,008 participants (9.6%) had DM. Compared to non-obese individuals with low ALT and GGT levels, the participants with high ALT and GGT levels had high ORs for DM in both obese (OR 4.06; 95% CI, 3.61-4.56) and non-obese groups (OR 2.19; 95% CI, 1.89-2.52). The obese group had high ORs for DM, even at low ALT and GGT levels., Conclusion: High ALT and GGT levels are associated with DM prevalence in obese and non-obese participants. This finding suggests that correcting ALT and GGT levels and controlling obesity are important for the prevention of DM.

Objective: No studies have demonstrated the association between urinary sodium-to-potassium (Na/K) ratio and all out-of-office blood pressure (BP) [home morning and evening BP (self-measured at home), and 24-h, daytime, and night-time ambulatory BP] in the same cohort. We aimed to assess, which type of out-of-office BP is more strongly associated with urinary Na/K ratio in the general population., Methods: This cross-sectional study was conducted in the general population of Ohasama, Japan. Home and ambulatory BP levels were measured, and 24-h urine samples were obtained from 875 participants (men, 25.5%; mean age, 60.1 years). The urinary Na/K ratio in the 24-h urine samples was calculated., Results: The median (interquartile range) urinary Na/K ratio was 4.19 (3.36-5.26). Significant positive trends of home morning, home evening, 24-h, and daytime SBP were observed across quartiles of urinary Na/K ratio (trend P  < 0.041; adjusted mean values between Q1 and Q4 of urinary Na/K ratio: 121.0-125.5 mmHg for home morning, 120.1-123.8mmhg for home evening, 121.6-123.4mmHg for 24-h, 127.5-129.5 mmHg for daytime). Urinary Na/K ratio was not significantly associated with office or night-time SBP and nocturnal BP fall (trend P > 0.13). In the model with both home morning or evening SBP and daytime SBP, only home SBP was significantly associated with urinary Na/K ratio (P < 0.048 for home SBP)., Conclusion: These findings suggest that urinary Na/K ratio might be more strongly associated with home BP than with 24-h and daytime BP but was not associated with night-time BP., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aims/introduction: Fat mass and fat-free mass affect glycated hemoglobin A1c (HbA1c) levels and blood glucose levels, respectively. The aim of the present study was to examine the association between the fat mass index and fat-free mass index with HbA1c., Materials and Methods: We carried out a cross-sectional study that included 3,731 men and 9,191 women aged ≥20 years, living in Miyagi Prefecture, Japan, who were not treated for diabetes. The fat mass index and fat-free mass index were calculated as fat mass and fat-free mass divided by the height squared, respectively. The indices were classified into sex-specific quartiles and combined into 16 groups. An analysis of covariance was used to assess associations between the combined fat mass index and fat-free mass index with HbA1c adjusted for potential confounders. The linear trend test was carried out by stratifying the fat mass index and fat-free mass index, entering the number as a continuous term in the regression model., Results: In multivariable models, a higher fat mass index was related to higher HbA1c levels in men and women in all fat-free mass index subgroups (P < 0.001 for linear trend). When we excluded the participants who had been identified as having diabetes, the fat-free mass index was also related to higher HbA1c levels in most fat mass index subgroups (P < 0.05 for linear trend)., Conclusions: Fat mass index was positively related to HbA1c levels. The fat-free mass index was also related to HbA1c levels when we excluded participants who had been identified as having have diabetes., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Predictive factors for intrahepatic cholangiocarcinoma in long-term follow-up of hepatolithiasis are unknown. We thus conducted a cohort study to investigate the predictive factors for developing intrahepatic cholangiocarcinoma in hepatolithiasis., Methods: This cohort is comprised of 401 patients registered in a nationwide survey of hepatolithiasis for 18 years of follow-up. Cox regression analysis was used to elucidate predictive factors for developing intrahepatic cholangiocarcinoma., Results: The median follow-up period of patients was 134 months. Twenty-two patients developed intrahepatic cholangiocarcinoma and all died. Identified independent significant factors were as follows: age 63 years or older (hazard ratio [HR] 3.344), residual stones at the end of treatment (HR 2.445), and biliary stricture during follow-up (HR 4.350). The incidence of intrahepatic cholangiocarcinoma in patients with three factors was significantly higher than that in patients with one or two factors. The incidence in the groups with one or two predictive factors was not different. In 88.9% of patients with both biliary stricture and intrahepatic cholangiocarcinoma, the duration between the diagnoses of biliary stricture and intrahepatic cholangiocarcinoma was ≥ 5 years. However, once intrahepatic cholangiocarcinoma developed, 77.8% of patients died within 1 year. Of 24 patients with no symptoms, no previous choledocoenterostomy, no signs of malignancy, no biliary stricture, and no treatment for hepatolithiasis during follow-up, only one developed intrahepatic cholangiocarcinoma., Conclusions: Regarding carcinogenesis, complete stone clearance and releasing biliary stricture can prevent the development of intrahepatic cholangiocarcinoma and improve the prognosis of hepatolithiasis., (© 2022. Japanese Society of Gastroenterology.)

The sodium-to-potassium (Na/K) ratio is known to be associated with blood pressure (BP). However, no reference value has been established since the urinary Na/K (uNa/K) ratio is known to have diurnal and day-to-day variations. Therefore, we investigated the number of days required to yield a better association between the morning uNa/K ratio and home BP (HBP) and determined a morning uNa/K ratio value that can be used as a reference value in participants who are not taking antihypertensive medication. This was a cross-sectional study using data from the Tohoku Medical Megabank Project Cohort Study. A total of 3122 participants borrowed HBP and uNa/K ratio monitors for 10 consecutive days. We assessed the relationship between the morning uNa/K ratio from 1 day to 10 days and home hypertension (HBP ≥ 135/85 mmHg) using multiple logistic regression models. Although a 1-day measurement of the morning uNa/K ratio was positively associated with home hypertension, multiple measurements of the morning uNa/K ratio were strongly related to home hypertension. The average morning uNa/K ratio was relatively stable after 3 days (adjusted odds ratio of home hypertension per unit increase in the uNa/K ratio for more than 3 days: 1.19-1.23). In conclusion, there was no threshold for the uNa/K ratio, and the morning uNa/K ratio was linearly associated with home hypertension. The Na/K ratio 2.0 calculated from the Dietary Reference Intakes for Japanese might be a good indication. Regarding the stability of the association between the morning uNa/K ratio and BP, more than 3 days of measurements is desirable., (© 2021. The Author(s).)

Background: GABAergic system dysfunction has been implicated in the etiology of schizophrenia and of cognitive impairments in particular. Patients with treatment-resistant schizophrenia (TRS) generally suffer from profound cognitive impairments in addition to severe positive symptoms, suggesting that GABA system dysfunction could be involved more closely in patients with TRS., Methods and Results: In the present study, exome sequencing was conducted on fourteen TRS patients, whereby four SNPs were identified on GAD1, GABBR1 and GABBR2 genes. An association study for five SNPs including these 4 SNPs and rs3749034 on GAD1 as then performed among 357 patients with TRS, 682 non-TRS patients and 508 healthy controls (HC). The results revealed no significant differences in allelic and/or genetic distributions for any of the five SNPs. However, several subanalyses in comparisons between schizophrenia and HC groups, as well as between the three groups, showed nominal-level significance for rs3749034 on GAD1 and rs10985765/rs3750344 on GABBR2. In particular, in comparisons of female subjects, rigorous analysis for rs3749034 showed a statistical difference between the schizophrenia and HC groups and between the TRS and HC groups., Conclusions: Several positive results in subanalyses suggested that genetic vulnerability in the GABA system to schizophrenia or TRS could be affected by sex or sampling area, and overall, that rs3749034 on GAD1 and rs10985765 on GABBR2 could be related to TRS. In the present study, only a few SNPs were examined; it is possible that other important genetic variants in other regions of GABA-related genes were not captured in this preliminary study., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: We determined the prevalence of current cigarette smokers and alcohol drinkers among cancer survivors and subjects with no history of cancer in Japan and compared the findings with nationally representative studies in other countries., Methods: We conducted a cross-sectional study of baseline data from a prospective cohort study. A self-administered questionnaire was surveyed during 2013-2015 with residents aged ≥20 years attending a community-based cardiometabolic screening program in Miyagi prefecture in north-eastern Japan. Subjects with past cancer histories were classified as cancer survivors. Sex-specific, age-standardized prevalence of current smokers, and drinkers were calculated. Age-adjusted prevalence ratios (PRs: the cancer survivors' rate divided by the rate of subjects with no history of cancer) and 95% confidence intervals (CIs) were estimated with log-binomial regressions., Results: 36,786 subjects, including 2760 cancer survivors, responded and provided usable information (58.9% of recruited subjects). For men, the age-standardized prevalence of current smokers and drinkers among survivors was 18.8% and 74.4%, respectively, with an age-adjusted PR (95%CI) of 0.76 (0.66-0.86, p < 0.001) and 0.95 (0.91-0.98, p = 0.002), respectively. For women, the figures were 6.1%, 37.9%, 0.84 (0.67-1.06, p = 0.138) and 0.96 (0.90-1.03, p = 0.313), respectively. The U.S., the U.K, and Australian studies generally showed no substantially lower prevalence of current smokers or drinkers in survivors than in subjects with no history of cancer (PR ≥ 0.75), while Korean studies did (PR < 0.75)., Conclusions: A considerable proportion of Japanese cancer survivors, especially men, remained currently smoking and drinking. Consistent with Western studies, the rates were not substantially lower than those among subjects with no history of cancer., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The projection from dopaminergic neurons to gamma-aminobutyric acid (GABA) interneurons in the prefrontal cortex is involved in the etiology of schizophrenia. The impact of interacting effects between dopamine signals and the expression of GABA on the clinical phenotypes of schizophrenia has not been studied. Since these interactions could be closely involved in prefrontal cortex functions, patients with specific alleles of these relevant molecules (which lead to lower or vulnerable genetic functions) may develop treatment-refractory symptoms. We conducted a genetic association study focusing on COMT and GAD1 genes for a treatment-resistant schizophrenia (TRS) group (n=171), a non-TRS group (n=592), and healthy controls (HC: n=447), and we examined allelic combinations specific to TRS. The results revealed that the percentage of subjects with Met allele of rs4680 on the COMT gene and C/C homozygote of rs3470934 on the GAD1 gene was significantly higher in the TRS group than the other two groups. There was no significant difference between the non-TRS group and HC groups. Considering the direction of functions of these single-nucleotide polymorphisms revealed by previous studies, we speculate that subjects with the Met/CC allelic combination could have a higher dopamine level and a lower expression of GABA in the prefrontal cortex. Our results suggest that an interaction between the dopaminergic signal and GABA signal intensities could differ between TRS patients and patients with other types of schizophrenia and healthy subjects., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Multiple sclerosis (MS) is a major demyelinating disease of the central nervous system; however, its exact mechanism is unknown. This study aimed to elucidate the profile of white blood cells (WBCs) in the acute phase of an MS attack. Sixty-four patients with MS at the time of diagnosis and 2492 age- and sex-adjusted healthy controls (HCs) were enrolled. Data regarding the blood cell counts were compared between the groups. The total WBC (p < 0.0001), monocyte (p < 0.0001), basophil (p = 0.0027), and neutrophil (p < 0.0001) counts were higher in the MS group than in the HC group, whereas the lymphocyte and eosinophil counts did not differ. Adjustments for the smoking status and body mass index yielded the same results. The total and differential WBC counts of the patients with MS did not correlate with the counts of T2 hyperintense brain lesions or the levels of neurological disturbance. In summary, patients with MS showed elevated counts of total WBCs, monocytes, basophils, and neutrophils at the time of diagnosis. However, the clinical relevance of these biomarkers in the context of the development and progression of MS remains unclear., (© 2021. The Author(s).)

Competing Interests: Junji Furuse: received honoraria from Eisai and is an editorial board member of Liver Cancer. Naohiro Okano received honoraria from Eisai. Other authors declare that they have no conflicts of interest or sources of funding for this manuscript.

After disasters, people are often forced to reconstruct or move to new residences. This study aimed to reveal the association between the types of reconstructed residences and psychosocial or psychiatric conditions among the population. A total of 1071 adult residents in a coastal town, whose houses were destroyed by the tsunami caused by the Great East Japan Earthquake, enrolled in the study five years after the disaster. The type of reconstructed post-disaster residences (reconstructed on the same site/disaster-recovery public condominium/mass-translocation to higher ground/privately moving to remote areas) and the current psychosocial indicators were investigated. The results revealed that individuals living in public condominiums showed significantly worse scores on the Lubben Social Network Scale-6 (p < 0.0001) and the Center for Epidemiologic Studies Depression Scale (p < 0.0001), and slightly worse scores on the Kessler Psychological Distress Scale (p = 0.035) and the Impact of Event Scale-Revised (p = 0.028). Lower psychosocial indicator scores in the public condominium group were more remarkable in younger adults aged < 65 years. Insomnia evaluated using the Athens Insomnia Scale was not different among the four residential types. In summary, residents moving into disaster-recovery public condominiums are likely to have less social interaction, be more depressed, and may need additional interventions., (© 2021. The Author(s).)

Background: A  higher body fat percentage is associated with hypertension, even in non-obese individuals. The difference in body composition may be related to hypertension. The fat mass index (FMI) and fat-free mass index (FFMI) are proposed indicators of body composition. This study aimed to examine the relationship of a combination of FMI and FFMI with hypertension., Methods: We conducted a cross-sectional study of 5,058 men and 11,842 women aged ≥ 20 years in the Miyagi Prefecture, northeastern Japan. The FMI and FFMI were calculated as the fat mass and fat-free mass divided by the height squared, respectively. The indices were classified into quartiles and combined into 16 groups. Hypertension was defined as casual blood pressure ≥ 140/90 mmHg and/or self-reported treatment for hypertension. Multivariable logistic regression models, adjusted for potential confounders, were used to assess the relationship of a combination of FMI and FFMI with hypertension., Results: Higher FMI was associated with hypertension in most of the FFMI subgroups. Similarly, a higher FFMI was associated with hypertension in most of FMI subgroups. For men, the association between FFMI and hypertension in the lowest FMI group was not significant., Conclusions: Reducing the FMI and FFMI may be important in preventing hypertension. For men, the relationship between the FFMI and hypertension in the lowest FMI group might be weak.

Purpose: Resection of liver cancer involving the paracaval portion (PC) of the caudate lobe is challenging because the PC is located deepest in the liver. This study aimed to elucidate the utility of two parenchymal-sparing approaches of limited resection and central hepatectomy for resecting tumors located in the PC., Methods: In 2018 and 2020, 12 out of 143 patients underwent hepatectomy for tumors located in the PC of the liver. In six patients, limited resection (LR) of the PC after full mobilization of the liver off the inferior vena cava (IVC) was performed for tumors excluding the hilar plate or large hepatic veins (large HVs), including major hepatic veins or thick short hepatic veins. In six patients, central hepatectomy (CH) using liver tunnel was performed for tumors involving or close to the hilar plate and/or large HVs., Results: During CH, the surgical view of the cranial side of the hilar plate was wide enough to perform combined resection of the large HVs in front of the IVC. Five of the six CHs were performed with resection of the LHVs. No LRs were accompanied with resection of the LHVs. The CH was associated with longer Pringle's time (76 min vs. 29.5 min, p = 0.015) and blood loss (1104 ml vs. 370 ml, p = 0.041). The preserved liver parenchyma volumes were 82% and 95% of the total liver volume after CH and LR, respectively., Conclusion: Our parenchymal-sparing approach for resection of liver cancer located in the PC is feasible for curative resection., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

No previous study has ever explored the association between coastal exposure and the mental health of residents in a post-disaster context. Therefore, we aimed to confirm whether there was an association between sea visibility and coastal proximity and the mental health of coastal residents a devastating tsunami. We targeted 15 coastal municipalities located in the Miyagi Prefecture, and obtained data from a community-based cohort study. The baseline survey was initiated 2 years after the 2011 Great East Japan Earthquake and Tsunami and the secondary survey was initiated 6 years after the disaster. We applied multilevel mixed-effects models to the longitudinal data. Our outcome measure was the Kessler Psychological Distress Scale (K6) score. We assessed the data collected from 2,327 respondents on both surveys as of April 2018 for this ongoing cohort study. We found that neither sea visibility nor coastal proximity was significantly associated with the recovery of mental health after the disaster. However, we found a distinctive trend of mental health recovery in people who lived alone with a sea view, indicating that visibility of the sea had a negative effect on their mental health immediately after the GEJET, but that the negative effect was subsequently eliminated., (© 2021. The Author(s).)

Purpose: Splenic vein (SV) ligation combined with portal vein (PV)/superior mesenteric vein (SMV) confluence resection during pancreaticoduodenectomy (PD) is reported to cause left-side portal hypertension (LPH). The purpose of this study was to present our technique of the SV reconstruction and to evaluate the surgical outcomes with/without SV ligation during PD., Methods: Twenty-four patients undergoing PD with PV and/or SMV resection and being followed over 4 months after surgery between March 2013 and December 2019 in our hospital were evaluated. Resection of the PV/SMV confluence were performed in 14, and SV reconstruction was successfully performed in 3. Presence of LPH was assessed by examining changes in splenic volume, newly venous collateral formation, and platelet counts before and 4-8 months after PD. Surgical technique is the direct anastomosis between SV and PV., Results: Splenic volume ratio was significantly higher in the SV ligation group (n = 11) than in the SV preservation group (n = 13) (median (range) 1.11 (0.57-1.62) vs. 1.68 (1.05-2.22), p < 0.01), but no significant differences were found in the incidence of newly formed venous collaterals or platelet counts between groups., Conclusion: SV ligation may represent the cause of LPH after PD combined with resection of PV/SMV confluence. Our simple procedure may help decrease the incidence of LPH., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Objectives: Safe and efficient methods for introducing clozapine to patients with treatment-resistant schizophrenia (TRS) are needed. We investigated risk factors for clozapine discontinuation in the early phase of its introduction., Methods: We conducted a nested case-control study at 14 psychiatric hospitals in Chiba, Japan. Data from pre-registered TRS patients were collected at 7 time points within 12 weeks before and after the start of clozapine introduction. We examined the demographic data, prior and concomitant psychotropic drugs, strategies for switching from prior antipsychotics, and blood test and Global Assessment of Function results. The Clinical Global Impression-Severity Scale was retrospectively scored at 12 weeks before and after clozapine introduction., Results: Of 228 patients, clozapine treatment was continued in 213 (93.4 %) and discontinued in 15 (6.6 %) patients within 12 weeks. Clinical symptoms were improved to mild symptoms with a response rate of 14.9 %. Prior antipsychotics and concomitant psychotropic drugs except for mood stabilizers were significantly decreased. Histories of smoking (OR = 3.32, 95 %CI: 1.11-9.93) and antipsychotic treatment at chlorpromazine-equivalent doses <1200 mg within the past 5 years (OR = 3.93, 95 %CI: 1.24-12.50), but not antipsychotic switching strategy, were associated with clozapine discontinuation. Eosinophilia was the most frequent reason for discontinuation (n = 3, 20 %) and was associated with concomitant valproate at 4 weeks after the introduction., Conclusion: Clozapine is an effective option for TRS patients (especially those treated with higher doses of prior antipsychotics) in Japan. Clinicians should be cautious about concomitant valproate in the early phase of clozapine introduction due to a high risk of eosinophilia., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Recently, a high urinary sodium-to-potassium (Na/K) ratio and reduced sleep efficiency, in addition to conventional risk factors (obesity and excess alcohol intake), have been identified as risk factors for hypertension. We estimated the population attributable fraction (PAF) for home hypertension due to these risk factors in a general Japanese population. We conducted a cross-sectional study including 1384 participants (393 men and 991 women) to estimate the odds ratio (OR) and 95% confidence interval (CI) for the presence of any of the conventional risk factors using multivariable logistic regression analyses. The models were adjusted for sex, age, smoking status, and log-transformed average daily steps. We also estimated the OR and 95% CI for the presence of any of the overall risk factors. Furthermore, we calculated the PAF due to these risk factors. The results showed that the prevalence of home hypertension was 39.0% (540/1384). The presence of any of the conventional risk factors, as well as any of the overall risk factors, was significantly associated with an increased prevalence of hypertension (OR 2.80, 95% CI 2.15-3.65; OR 2.50, 95% CI 1.93-3.22, respectively). The PAF for hypertension due to the presence of any of the conventional risk factors and the PAF due to the presence of any of the overall risk factors were 30.2% and 39.0%, respectively. In conclusion, the impact of the overall risk factors, including the urinary Na/K ratio and sleep efficiency, on home hypertension was higher than that of conventional risk factors alone. The management of the urinary Na/K ratio and sleep efficiency as well as conventional risk factors might be important in the management of blood pressure.

Background: To clarify whether double-volume peritoneal lavage can decrease the risk of clinically relevant postoperative pancreatic fistula after pancreaticoduodenectomy., Materials and Methods: Forty-nine patients who underwent pancreaticoduodenectomy and intraoperative peritoneal lavage using 6000 mL of saline before abdominal closure were studied retrospectively. Bacterial cultures of the lavage fluid were taken twice, after irrigation using 3000 mL of saline and then after an additional 3000 mL of saline. Bacterial culture of the drainage fluid was taken on day 1, and the relationship between the results of bacterial cultures and clinically relevant postoperative pancreatic fistula was examined., Results: Double amount of peritoneal lavage significantly decreased the incidence of positive bacterial cultures than single amount of peritoneal lavage (45% vs. 29%, P < .05). Multivariate analysis showed that positive bacterial culture of drainage fluid on day 1 and main pancreatic duct size (<3 mm) were independent risk factors for clinically relevant postoperative pancreatic fistula. A positive bacterial culture of the final lavage fluid and preoperative biliary drainage were independent factors related to a positive bacterial culture on day 1., Discussion: A positive bacterial culture on day 1 is an independent risk factor for clinically relevant postoperative pancreatic fistula during pancreaticoduodenectomy. Double-volume intraperitoneal lavage may be effective for reducing the incidence of clinically relevant postoperative pancreatic fistula.

Objective: This study aims to evaluate the long-term impact of living in post-disaster prefabricated temporary housing on social interaction activities and mental health status., Methods: A total of 917 adult residents in a coastal town, whose residences were destroyed by the tsunami caused by the Great East Japan Earthquake (GEJE), were enrolled for the assessment held five years after the disaster. They answered questions about their experience and consequence of living in prefabricated temporary housing after the disaster. Their present scores on five types of self-reported measures regarding the psychosocial or psychiatric status and their present and recalled social interaction activities were cross-sectionally collected., Results: A total of 587 (64.0%) participants had a history of living in prefabricated temporary housing, while the other 330 (36.0%) had not. The prevalence of social interaction activities significantly decreased after the GEJE. However, the experience of living in prefabricated temporary housing did not adversely affect the subsequent social interaction activities or mental conditions of the participants five years after the disaster., Conclusions: Living in post-disaster prefabricated temporary housing may not negatively impact subsequent psychosocial conditions or social interaction activities five years later.

Background: Excision of the mesopancreas with lymphadenectomy is an important component of pancreatoduodenectomy. However, the optimal extent of lymphadenectomy remains unclear. Furthermore, accurate description of the mesopancreatic lymphatic pathways is difficult, probably because of the complex anatomy. Intestinal derotation simplifies the anatomy and facilitates both examination of lymphatic flow and the surgical procedure. The aim of this study was to evaluate lymphatic flow in the mesopancreas using indocyanine green fluorescence imaging with an intestinal derotation technique, and to clarify the optimal extent of mesopancreas excision and lymphadenectomy in pancreatoduodenectomy., Methods: Indocyanine green solution (2.5 × 10 -3  mg) was injected into the pancreatic head parenchyma. After intestinal derotation, the spread of indocyanine green was observed using near-infrared imaging., Results: Participants comprised 10 patients who underwent pancreatoduodenectomy for periampullary neoplasms. With indocyanine green fluorescence imaging, 9 of the 10 patients showed lymphatic flow from the pancreatic head to the superior mesenteric artery via the inferior pancreaticoduodenal artery and first jejunal artery (but not via the second and more distant arteries), with eventual drainage into the paraaortic region., Conclusions: Lymphatic pathways from the pancreatic head were connected to the superior mesenteric artery via the inferior pancreaticoduodenal artery and first jejunal artery. Excision of the mesopancreas with the inferior pancreaticoduodenal artery and first jejunal artery while preserving the second or more distant arteries appears optimal in pancreatoduodenectomy for periampullary malignancies.

Background: Major reasons for long-term care insurance certification in Japan are stroke, dementia, and fracture. These diseases are reported to be associated with calcium intake. This study examined the association between calcium intake and impaired activities of daily living (ADL) using the data from NIPPON DATA90, consisting of representative sample of the Japanese population., Methods: A population-based nested case-control study was performed. A baseline survey was conducted in 1990, followed by ADL surveys of individuals ≥65 years old in 2000. Individuals with impaired ADL and selected age- and sex-matched controls were then identified. We obtained 132 pairs. Calcium intake was energy-adjusted using the residual method. The association between calcium intake and impaired ADL was examined using conditional logistic regression models. To assess the accuracy of the estimates, we conducted bootstrap analyses., Results: The adjusted odds ratios (ORs) for impaired ADL compared with the group with a calcium intake of <476 mg/day were 0.72 (95% confidence interval [CI], 0.37-1.40) for the 476-606 mg/day group and 0.44 (95% CI, 0.21-0.94) for the ≥607 mg/day group in 2000 (P for linear trend = 0.03). After the bootstrap analyses, the inverse relationship unchanged (median OR per 100-mg rise in calcium intake, 0.87 [1,000 resamplings]; 95% CI, 0.76-0.97)., Conclusions: After bootstrap analyses, calcium intake was inversely associated with impaired ADL 10 years after the baseline survey.

Recently, the sodium (Na)/potassium (K) ratio was reported to be associated with blood pressure (BP). A Na/K ratio self-monitoring device using spot urine was established recently. Here, we assessed whether the urinary Na/K ratio change measured using the Na/K device was associated with BP change in a health checkup setting. We targeted 12,890 participants who attended the health checkup in Tome City, Miyagi between 2017 and 2018. Tome City introduced urinary Na/K ratio measurements during health checkups since 2017. For each year, we compared the baseline characteristics according to the urinary Na/K ratio and BP level. We assessed the relationship between change in urinary Na/K ratio and BP change using multiple regression analyses adjusted for age, sex, and change in body mass index (BMI) and alcohol intake. The average urinary Na/K ratio was significantly lower in 2018 than in 2017 (5.4 ± 3.0 to 4.9 ± 2.2, P < 0.01). The systolic BP of the participants in 2018 (130.9 ± 17.4 mmHg) was lower than that in 2017 (132.1 ± 17.9 mmHg). Moreover, the change in systolic BP and diastolic BP was positively associated with the change in urinary Na/K ratio. In conclusion, the association of the change in urinary Na/K ratio with hypertension and changes in systolic and diastolic BP can be explained by a change in alcohol intake, BMI, and urinary Na/K ratio. Therefore, measuring the urinary Na/K ratio in community settings is a potential population approach for counteracting hypertension.