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Background: Recent studies about inter-reporter differences and patient-reported outcomes (PROs) in childhood cancer from Western countries showed that caregiver proxy reports tend to overestimate symptom burdens in comparison with children's self-reports. However, the results from Western countries may not be generalizable to Asian countries., Methods: This paper is a secondary analysis of a validation study of the Japanese pediatric version of the Memorial Symptom Assessment Scale including 88 dyads of children aged 7-12 years and 74 dyads of children aged 13-18 years and their caregivers. The study assessed the inter-reporter differences of eight and 31 symptom burdens calculated as symptom scores in children aged 7-12 years and 13-18 years, respectively, and the association between inter-reporter differences and the characteristics of children and caregivers., Results: The majority of children and caregivers scored equally at the dyadic level for almost all symptoms. However, 37.5% of symptoms in children aged 7-12 years and 10.0% of symptoms in children aged 13-18 years showed significant inter-reporter differences, suggesting a general tendency of caregivers to underestimate their children's symptom burden. The caregiver's age was the characteristic most frequently associated with magnitude of inter-reporter differences., Conclusions: Caregiver proxy reports may be a reliable source of PROs in Japanese children with cancer, as self-reported and caregiver proxy-reported symptom burdens were generally concordant. However, as some significant inter-reporter differences were observed, an effort should be made within the medical community to evaluate the parent-child relationship to minimize inter-reporter differences and achieve better symptom management., (© 2024 Japan Pediatric Society.)

Background/aims: Colorectal adenomas are precursor lesions of globally increasing colorectal cancer. Hence, a high adenoma detection rate in colonoscopy is pivotal. We investigated the clinical impact of stratified colonoscopy observation time combined with observation time/intubation time ratio on the detection of colorectal adenomas., Materials and Methods: We conducted a single-center retrospective study including 369 consecutive patients who underwent colonoscopy following fecal immunochemical tests between May 2021 and April 2022. The primary outcome measure was the impact of the stratified observation time and observation time/ intubation time ratio (category 1: <6.0 minutes and <1.0, category 2: <6.0 minutes and ≥1.0, category 3: ≥6.0 minutes and <1.0, and category 4: ≥6.0 minutes and ≥1.0) on adenoma detection rate., Results: Cecum intubation was obtained in 367 patients (99.5%). Adenomas were detected in 226 patients (61.2%). From the univariate analysis, age ≥53 years, habitual alcohol intake, colonoscopy attachment (+), and observation time with observation time/intubation time ratio categories 3 and 4 were determined as significant factors for adenoma detection rate. From the logistic regression analysis, age ≥ 53 years (odds ratio: 4.86, 95% CI: 2.25-10.52), habitual alcohol intake (odds ratio: 2.26, 95% CI: 1.33-3.82), category 3 (odds ratio: 3.66, 95% CI: 1.81-7.45), and category 4 (odds ratio: 5.60, 95% CI: 2.92-10.73) were significant factors for adenoma detection rate., Conclusion: We propose the observation time with observation time/intubation time ratio combined benchmark (with categories' thresholds based on observation time >6 minutes and scope withdrawal time exceeding intubation time [observation time/intubation time ratio > 1]) as a novel colonoscopy quality indicator. These findings represent an important educational message for endoscopists.

Background: Reduced or delayed medical follow-ups have been reported during the COVID-19 pandemic, which may lead to worsening clinical outcomes for patients with diabetes. The Japanese government granted special permission for medical institutions to use telephone consultations and other remote communication modes during the COVID-19 pandemic., Objective: We aimed to evaluate changes in the frequency of outpatient consultations, glycemic control, and renal function among patients with type 2 diabetes before and during the COVID-19 pandemic., Methods: This is a retrospective single-cohort study conducted in Tokyo, Japan, analyzing results for 3035 patients who visited the hospital regularly. We compared the frequency of outpatient consultations attended (both in person and via telemedicine phone consultation), glycated hemoglobin A 1c (HbA 1c ), and estimated glomerular filtration rate (eGFR) among patients with type 2 diabetes mellitus during the 6 months from April 2020 to September 2020 (ie, during the COVID-19 pandemic) with those during the same period of the previous year, 2019, using Wilcoxon signed rank tests. We conducted a multivariate logistic regression analysis to identify factors related to the changes in glycemic control and eGFR. We also compared the changes in HbA 1c and eGFR from 2019 to 2020 among telemedicine users and telemedicine nonusers using difference-in-differences design., Results: The overall median number of outpatient consultations attended decreased significantly from 3 (IQR 2-3) in 2019 to 2 (IQR 2-3) in 2020 (P<.001). Median HbA 1c levels deteriorated, though not to a clinically significant degree (6.90%, IQR 6.47%-7.39% vs 6.95%, IQR 6.47%-7.40%; P<.001). The decline in median eGFR was greater during the year 2019-2020 compared to the year 2018-2019 (-0.9 vs -0.5 mL/min/1.73 m2; P=.01). Changes in HbA 1c and eGFR did not differ between patients who used telemedicine phone consultations and those who did not. Age and HbA 1c level before the pandemic were positive predictors of worsening glycemic control during the COVID-19 pandemic, whereas the number of outpatient consultations attended was identified as a negative predictor of worsening glycemic control during the pandemic., Conclusions: The COVID-19 pandemic resulted in reduced attendance of outpatient consultations among patients with type 2 diabetes, and these patients also experienced deterioration in kidney function. Difference in consultation modality (in person or by phone) did not affect glycemic control and renal progression of the patients., (©Akiko Sankoda, Yugo Nagae, Kayo Waki, Wei Thing Sze, Koji Oba, Makiko Mieno, Masaomi Nangaku, Toshimasa Yamauchi, Kazuhiko Ohe. Originally published in JMIR Diabetes (https://diabetes.jmir.org), 21.11.2023.)

Importance: Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US., Objective: To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes., Design, Setting, and Participants: Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021., Exposures: The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR)., Main Outcomes and Measures: The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses., Results: Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years])., Conclusions and Relevance: In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations.

Background: High lipoprotein (a) level is an established cardiovascular risk, but its association with non-cardiovascular diseases, especially cancer, is controversial. Serum lipoprotein (a) levels vary widely by genetic backgrounds and are largely determined by the genetic variations of apolipoprotein (a) gene, LPA. In this study, we investigate the association between SNPs in LPA region and cancer incidence and mortality in Japanese., Methods: A genetic cohort study was conducted utilizing the data from 9923 participants in the Japan Public Health Center-based Prospective Study (JPHC Study). Twenty-five SNPs in the LPAL2-LPA region were selected from the genome-wide genotyped data. Cox regression analysis adjusted for the covariates and competing risks of death from other causes, were used to estimate the relative risk (hazard ratios (HR) with 95% confidence intervals (CI)) of overall and site-specific cancer incidence and mortality, for each SNP., Results: No significant association was found between SNPs in the LPAL2-LPA region and cancer incidence or mortality (overall/site-specific cancer). In men, however, HRs for stomach cancer incidence of 18SNPs were estimated higher than 1.5 (e.g., 2.15 for rs13202636, model free, 95%CI: 1.28-3.62) and those for stomach cancer mortality of 2SNPs (rs9365171, rs1367211) were estimated 2.13 (recessive, 95%CI:1.04-4.37) and 1.61 (additive, 95%CI: 1.00-2.59). Additionally, the minor allele for SNP rs3798220 showed increased death risk from colorectal cancer (CRC) in men (HR: 3.29, 95% CI:1.59 - 6.81) and decreased CRC incidence risk in women (HR: 0.46, 95%CI: 0.22-0.94). Minor allele carrier of any of 4SNPs could have risk of prostate cancer incidence (e.g., rs9365171 dominant, HR: 1.71, 95%CI: 1.06-2.77)., Conclusions: None of the 25 SNPs in the LPAL2-LPA region was found to be significantly associated with cancer incidence or mortality. Considering the possible association between SNPs in LPAL2-LPA region and colorectal, prostate and stomach cancer incidence or mortality, further analysis using different cohorts is warranted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Psoriasis is an immune-mediated chronic inflammatory disease that predominantly affects the skin and joints. Systemic therapies are required for patients with moderate-to-severe psoriasis, and biologics can provide significant symptomatic improvement. Computed tomography (CT) analysis is recommended before and after biologic therapy to exclude the possibility of comorbid infections and malignancies; incidental findings are often detected in asymptomatic patients. In this study, we analyzed the common incidental findings on CT in 227 patients with psoriasis on biologic therapy and 219 living-kidney transplant donors at our hospital. Incidental findings on CT were observed in 176 (77.5%) patients with psoriasis. The most common were fatty liver (82 patients, 36.1%), urolithiasis (54 patients, 23.8%), pulmonary lesions (47 patients, 20.7%), gallstones or postoperative gallstones (38 patients, 16.7%), liver cysts (36 patients, 15.9%), renal cysts (33 patients, 14.5%), and colonic diverticulum (22 patients, 9.7%), which were observed in 38 (17.4%), eight (3.7%), 68 (31.1%), 12 (5.5%), 58 (26.5%), 88 (40.2%), and 10 (4.6%) donors, respectively. The prevalence of fatty liver, urolithiasis, gallstones, and postoperative gallstones was significantly higher in patients with psoriasis. Multivariate logistic regression showed that psoriasis was a risk factor for fatty liver disease, urolithiasis, and gallstones. Currently, incidental findings on CT in patients with psoriasis have not been well studied. The results of this survey will lead to increased awareness of the incidental findings on CT as a complication of psoriasis., (© 2023 Japanese Dermatological Association.)

Introduction: This study aimed to retrospectively examine the drug survival of tumor necrosis factor (TNF)-alpha inhibitors and switched subsequent biologic agents after discontinuation of TNF inhibitors., Methods: This real-world setting study was conducted at a single academic center. We included patients who were treated with adalimumab (n = 111), certolizumab pegol (n = 12), and infliximab (n = 74) at Jichi Medical University Hospital from 1 January 2010 to 31 July 2021., Results: No significant differences were noted in drug survival between the three TNF inhibitors. The 10-year drug survival rate for adalimumab and infliximab was 14% and 18%, respectively. Of the patients who discontinued TNF inhibitors for any reason (n = 137), 105 chose biologics as their subsequent treatment. The subsequent biologics included 31 cases of TNF inhibitors (adalimumab in 20, certolizumab pegol in 1, and infliximab in 10), 19 of interleukin-12/23 inhibitor (ustekinumab), 42 of interleukin-17 inhibitors (secukinumab in 19, brodalumab in 9, and ixekizumab in 14) and 13 of interleukin-23 inhibitors (guselkumab in 11, risankizumab in 1, and tildrakizumab in 1). Cox proportional hazards analysis for the subsequent drugs in cases of discontinuation due to inadequate efficacy revealed that female sex was a predictor of drug discontinuation (hazard ratio 2.58, 95% confidence interval 1.17-5.70) and that taking interleukin-17 inhibitors rather than TNF inhibitors was a predictor of drug persistence (hazard ratio 0.37, 95% confidence interval 0.15-0.93)., Conclusions: Interleukin-17 inhibitors may be a favorable option for patients who need to switch from TNF inhibitors due to inadequate efficacy. However, this study is limited by the small number of cases and its retrospective design., (© 2023. The Author(s).)

Objective: We investigated the efficacy of the Delirium Team Approach program for delirium prevention after cardiovascular surgery., Methods: We retrospectively investigated 256 patients who underwent cardiac or thoracic vascular surgery between May 2017 and May 2020. We compared the outcomes before and after implementation of the Delirium Team Approach program in December 2018. The program included the following components: (a) educational sessions for the medical team regarding delirium and its management, (b) review of preprinted physician orders for insomnia and agitation, and (c) routine screening for delirium. We investigated the early outcomes and effects of the Delirium Team Approach program on postoperative delirium., Results: The incidence of postoperative delirium significantly decreased from 53.3% to 37.0% after implementation of the Delirium Team Approach program (P = .008). Although no intergroup differences were observed in the rates of stroke and reexploration for bleeding, the length of intensive care unit stay and the overall length of postoperative hospital stay were shorter in the postintervention group. Hospital costs, excluding surgery, and the cost during intensive care unit stay were lower in the postintervention group. Multivariable analysis showed that the Delirium Team Approach program was associated with a reduction in postoperative delirium (odds ratio, 0.38; 95% confidence interval, 0.21-0.67; P = .001). Other predictors of delirium included age, dementia, chronic kidney disease, and intubation time. After risk adjustment using propensity score matching, the rate of postoperative delirium was lower in the postintervention group., Conclusions: Implementation of the Delirium Team Approach program was associated with a lower incidence of postoperative delirium in patients who underwent cardiovascular surgery., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: This trial evaluated the superiority of intraoperative wound irrigation (IOWI) with aqueous povidone-iodine (PVP-I) compared with that with saline for reducing the incidence of surgical site infection (SSI)., Background: IOWI with aqueous PVP-I is recommended for the prevention of SSI by the World Health Organization and the Centers for Disease Control and Prevention, although the evidence level is low., Methods: This single institute in Japan, prospective, randomized, blinded-endpoint trial was conducted to assess the superiority of IOWI with aqueous PVP-I in comparison with IOWI with saline for reducing the incidence of SSI in clean-contaminated wounds after gastroenterological surgery. Patients 20 years or older were assessed for eligibility, and the eligible participants were randomized at a 1:1 ratio using a computer-generated block randomization. In the study group, IOWI was performed for 1 minute with 40 mL of aqueous 10% PVP-I before skin closure. In the control group, the procedure was performed with 100 mL of saline. Participants, assessors, and analysts were masked to the treatment allocation. The primary outcome was the incidence of incisional SSI in the intention-to-treat set., Results: Between June 2019 and March 2022, 941 patients were randomized to the study group (473 patients) or the control group (468 patients). The incidence of incisional SSI was 7.6% in the study group and 5.1% in the control group (risk difference 0.025, 95% CI -0.006 to 0.056; risk ratio 1.484, 95% CI 0.9 to 2.448; P =0.154)., Conclusion: The current recommendation of IOWI with aqueous PVP-I should be reconsidered., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Endoscopic balloon dilation (EBD) is an effective, minimally invasive treatment for Crohn's disease (CD) related intestinal strictures. However, restenosis frequently occurs and requires repetitive EBD or surgical resection. Since previous studies could not evaluate restenosis based on stricture diameter, factors affecting restenosis after EBD were unclear. This study aimed to identify these factors by precisely measuring the diameter of small intestinal strictures in patients with CD., Methods: This single-center retrospective study enrolled patients with CD with de novo small intestinal strictures who underwent two double-balloon enteroscopy sessions (EBD and follow-up) between January 2016 and October 2021. Clinical and endoscopic data were obtained from electronic medical records. A calibrated small-caliber-tip transparent hood was used to precisely measure stricture diameters. Multivariate analysis was performed to identify factors associated with restenosis., Results: Forty-eight patients (37 male) were analyzed. The total number of strictures detected decreased from 162 to 143. The mean diameter of all strictures and the narrowest stricture in each patient increased significantly from 8.6 to 9.8 mm and from 7.6 to 8.7 mm, respectively. Thirty-two (67%) patients developed endoscopic restenosis. Multivariate analysis showed that the presence of ulcers at the follow-up session was a risk factor for restenosis (odds ratio 9.4, p = 0.01). Patients with complete mucosal healing at both sessions ( n = 21) showed significant improvement in the narrowest stricture (+1.7 mm, p = 0.001)., Conclusions: Maintenance of complete mucosal healing is significantly associated with avoiding restenosis after EBD in CD-related small intestinal strictures., Competing Interests: Hironori Yamamoto has patents for the calibrated small‐caliber‐tip transparent hood. Hironori Yamamoto has patents for double‐balloon endoscopy and a consultant relationship with Fujifilm. Tomonori Yano and Hirotsugu Sakamoto have received research funding and honoraria from Fujifilm. No other authors have personal financial relationships with a commercial entity producing healthcare‐related products and/or services relevant to this article., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

The predominant histological subtype of breast mucinous carcinoma in older women is type B (hypercellular type), and, in younger women, it is type A (hypocellular type). The characteristics of mucinous carcinomas of the same histological subtype may differ between older and younger women. This study aims to systematically clarify the pathological/immunohistochemical features of mucinous carcinomas. A total of 21 surgical cases of mucinous carcinoma (type A/B: 9/12 cases) in the older group (≥65 years) and 16 cases (type A/B: 14/2 cases) in the younger group (≤55 years) (n = 37) were included. Gross cystic disease fluid protein-15 (GCDFP-15) and eight other markers were used for immunostaining. The GCDFP-15-positive rate in the older group was high regardless of the histological subtype (type A, 77.8%; type B, 91.7%). The GCDFP-15 positivity in the older group was significantly higher than that in the younger group (p < 0.001 for Allred score). Among type A, GCDFP-15 positivity was significantly higher in the older group than in the younger group (p = 0.042 for the Allred score and p = 0.007 for the positivity rate). The present results suggest that GCDFP-15 expression characterizes mucinous carcinomas in older women.

Rapid deployment valve has expanded surgical indication for high-risk patients with aortic stenosis despite its accommodated risk for conduction disorder (CD). The purpose of this study was to evaluate the degree of oversizing in association with postoperative CD. During June 2019 to September 2021, 25 patients underwent aortic valve replacement with Edwards INTUITY. Device size selection was evaluated intraoperatively using provided sizers. Oversizing was evaluated retrospectively by measuring the difference of the dimension of the annulus and left ventricular outflow tract (LVOT) compared to the dimensions of the device used by preoperative-computed tomography. Although there was no incidence of pacemaker implantation, seven patients (28.0%) experienced CD after surgery. There was no difference in device area and annulus area (CD: - 37 ± 22.7 mm 2 vs. no CD: - 56 ± 63.6 mm 2 , p = 0.47), and device circumference and annulus circumference (CD: - 4.4 ± 2.77 mm vs. no CD: - 6.9 ± 5.60 mm, p = 0.26) in patients with and without CD. However, there was a significant difference in area of the device skirt and sub-annular area at the LVOT (CD: 114 ± 28.4 mm 2 vs. no CD: - 8 ± 80.0 mm 2 , p < 0.001), and circumference of device skirt and the LVOT (CD: 3.9 ± 2.08 mm vs. no CD: - 4.6 ± 5.24 mm, p < 0.001) between the two groups. Receiver operating characteristic curve analysis showed that an area difference of 77.7 mm 2 and circumference difference of 0.91 mm at LVOT were associated with postoperative CD with specificities of 0.83, 0.78 and sensitivity of 1.0, 1.0, respectively. Preoperative measurement of the LVOT may be useful in evaluating the risk of postoperative CD in patients receiving rapid deployment valve., (© 2021. The Japanese Society for Artificial Organs.)

Interstitial lung disease (ILD) carries a risk for severe pneumonia in patients with rheumatoid arthritis (RA). Bronchiectasis, another risk of severe pneumonia, has not been well elucidated in RA. We investigated the types of respiratory diseases in RA and correlated them to severe pneumonia during the course of treatment using biologic DMARDs (bDMARDs), with special attention to bronchiectasis and ILD. RA patients were examined by computed tomography before starting bDMARDs and divided into three groups: normal, bronchiectasis and ILD. The log-rank test and Dunnett's multiple comparisons test were employed for the statistical analysis. Among 424 patients, 350 were categorized as normal, 32 as having bronchiectasis, and 42 as having ILD. Two in the normal group, three in the bronchiectasis group and four in the ILD group developed severe pneumonia. The log-rank test showed a significant difference among the three groups (p < 0.0001). The pneumonia-free rates in the bronchiectasis and ILD groups were significantly lower than the normal group, respectively, with Dunnett's multiple comparison test (p < 0.0001). This study suggests that the bronchiectasis that occurs in RA carries a risk of severe pneumonia during treatment with bDMARDs that is comparable to ILD., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The purpose of this study was to investigate the changes in pulse wave velocity (PWV) after aortic arch repair and to evaluate possible perioperative factors associated with an increase in PWV., Methods: Eighty-nine patients with preoperative and postoperative PWV measurements who underwent surgical treatment for true aortic arch aneurysm were included in the study. The patients were treated by prosthetic graft replacement with or without the frozen elephant trunk technique or by hybrid surgery with a stent graft. Changes in PWV and perioperative factors were evaluated., Results: Fifty-one patients were treated by prosthetic graft replacement; 22 patients were treated with the frozen elephant trunk procedure; and 16 patients were treated by hybrid surgery. A significant increase in PWV was observed in patients undergoing surgical treatment for aortic arch aneurysm regardless of the types of operations performed (all treatments: before, 1797 ± 397.8 cm/s vs after, 2061 ± 600.4 cm/s, P < 0.001; graft replacement: before, 1769 ± 398.1 cm/s vs after, 1895 ± 459.0 cm/s, P = 0.004; frozen elephant trunk procedure: before, 1911 ± 461.9 cm/s vs after 2307 ± 826.9 cm/s, P = 0.005; hybrid surgery: before, 1732 ± 273.3 cm/s vs after, 2254 ± 484.6 cm/s, P < 0.001). Differences in PWV were largest in patients treated with hybrid surgery and lowest in those treated with graft replacement (P = 0.002). In univariate analysis, an increase in PWV was positively correlated with treatment length (r = 0.41; P < 0.001); the use of a postoperative beta blocker was associated with a smaller increase in postoperative PWV (with: 165.0 ± 371.92 cm/s vs without: 439.4 ± 530.38 cm/s, P = 0.005). Multivariate analysis suggested that treatment length (coefficient 3.31, 95% confidence interval 0.056-6.562, P = 0.046) and postoperative beta blocker (coefficient -220.08, 95% confidence interval -401.972 to -38.183, P = 0.018) were factors independently associated with changes in PWV., Conclusions: There was a significant increase in PWV after aortic arch repair. Treatment length and use of postoperative beta blockers were factors associated with changes in postoperative PWV. Minimizing the treatment length and using postoperative beta blockers may attenuate the effects of prostheses on postoperative PWV., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Purpose: We investigated factors contributing to coagulopathy in patients with acute type A aortic dissection (ATAAD) and coagulopathy's influence on patient outcomes., Methods: We grouped 420 patients who underwent ATAAD repair-none under anticoagulation therapy or with liver disease-by the prothrombin time-international normalized ratio (PT-INR) at admission:  <  1.2 (no coagulopathy, n  =  371), 1.2-1.49 (mild coagulopathy, n  =  33), or  ≥  1.5 (severe coagulopathy, n  =  16). We then compared the clinical presentation, dissection morphology, and outcomes among the groups. We assessed the PT-INR in relation to the preoperative hemodynamics and searched for factors predictive of a PT-INR  ≥  1.2., Results: The transfusion volume and operation time were increased among patients with coagulopathy (P  <  0.05). The in-hospital mortality (15.2-37.5% vs. 5.1%, P  < 0.001) and 5-year survival (61.1-74.4% vs. 87.6%) were relatively poor for these patients. The median PT-INR was 1.03 (0.97-1.1) for patients with stable hemodynamics (n  =  318), 1.11 (1.02-1.21) for those in shock (blood pressure  <  80 mmHg) not given cardiopulmonary resuscitation (CPR) (n  =  81), and 1.1 (1.0-1.54) for those in shock given CPR (n  =  21) (P  < 0.001). A multivariable analysis identified shock (P  <  0.001), a partially thrombosed false lumen (P  =  0.006), and mesenteric malperfusion (P  =  0.016) as predictive variables., Conclusions: Shock, a partially thrombosed false lumen, and mesenteric malperfusion appear to be predictive of dissection-related coagulopathy, which influences outcomes negatively., (© 2021. The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: In Japan, donations after circulatory death kidney transplantation are widely performed due to legislation delays. The number of donations after brain death kidney transplantations is increasing, but the target remains unmet. We reviewed the outcomes of donation after circulatory death in Japan., Methods: We analyzed 2923 deceased kidney transplantations (2239: donation after circulatory death (DCD), 684: donation after brain death (DBD)) performed in Japan from 2000 to 2019. The outcomes of the DCD and DBD groups were compared. We examined the risk factors for graft loss in the DCD group., Results: The 5-year patient survival and death-censored graft survival rates of the DCD group, obtained by propensity score matching, were 93.6% and 95.2%, respectively, which were equivalent to 94.2% and 93.8%, respectively, obtained in the DBD group. Older donors (≥ 50 years) and prolonged cold ischemia time (≥ 12 h) were risk factors for graft loss; in the presence of these, graft survival was lower in the DCD group., Conclusions: Older donors and prolonged cold ischemia time reduced graft survival in the DCD group. Proper evaluation of donors and careful preparation for transplant surgery are, therefore, essential to ensure good transplant outcomes., (© 2021. Japanese Society of Nephrology.)

Background: Neoadjuvant systemic therapy (NST) induces tumor shrinkage and boosts the chance of breast-conserving thearpy (BCT) in patients with breast cancer. However, only a few trials have evaluated the effect of NST in conversion from BCT ineligibility to BCT eligibility in HER2-positive breast cancer., Methods: We conducted the surgical sub-study of a phase II randomized trial, which compared standard neoadjuvant treatment or an experimental treatment modified according to the interim Ki-67 evaluation in women with stage II or III HER2-positive breast cancer. The treating surgeons assessed eligibility for BCT before and after NST. We evaluated the change in BCT eligibility following NST. We also analyzed the type of surgery performed and the success rate of BCT., Results: Two hundred six patients were included in this study. Of these, 44.0% were considered BCT candidates at baseline, while 69.8% were deemed eligible for BCT after NST (P < 0.001). Among non-BCT candidates at baseline, 46% successfully converted to BCT candidates. Of 139 patients deemed eligible for BCT following NST, 84.2% attempted BCT, and successful BCT, defined as tumor-free at all surgical margins, was achieved in 96.8% of patients. Different treatment arms did not affect the rate of post-NST BCT eligibility (70.0% vs 69.7%)., Conclusions: This study demonstrated that NST resulted in an absolute increase of 25.8% in the rate of BCT eligibility in HER2-positive breast cancer. About a half of non-BCT candidates converted to BCT candidates. BCT was successful in most patients who attempted BCT. There were still patients who chose mastectomy even though they were deemed eligible for BCT. Patients considered BCT-ineligible due to large tumor size most likely converted to BCT-eligible with NST. On the other hand, NST had less impact on the surgical indication of patients with multicentric disease or probable poor cosmetic outcome., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: We investigated the etiology and impact on outcomes of polycystic kidney disease in patients with abdominal aortic aneurysm., Methods: Eight-hundred patients who underwent open (n = 603) or endovascular aortic repair (n = 197) were divided into three groups: no cyst (n = 204), non-polycystic kidney (n = 503), and polycystic kidney (≥ 5 cysts in the bilateral kidneys, n = 93). The characteristics and outcomes were compared among the groups., Results: In the polycystic kidney group, the age was increased and the proportions of patients with male sex, hypertension, and estimated glomerular filtration rate < 30 mL/min/1.73 m 2 were greater. The overall hospital mortality rates were similar. The incidence of acute kidney injury after elective open aortic repair was increased in the polycystic kidney group (12%, 17%, and 29%, P = 0.020). In the polycystic kidney group, 80 patients did not have renal enlargement or a family history of renal disease, while 13 (corresponding to 1.6% [13/800] of the overall patients), had renal enlargement, suggesting the possibility of hereditary polycystic kidney disease., Conclusions: In our cohort, 1.6% of the patients with abdominal aortic aneurysm who underwent surgery were at risk of hereditary polycystic kidney disease. Polycystic kidney disease was associated with acute kidney injury after open aortic repair.

Semen quality is affected by environmental factors, endocrine function abnormalities, and genetic factors. A GWAS recently identified ERBB4 at 2q34 as a genetic locus associated with sperm motility. However, GWASs for human semen volume and sperm concentration have not been conducted. In addition, testis size also reportedly correlates with semen quality, and it is important to identify genes that affect testis size. Reproductive hormones also play an important role in spermatogenesis. To date, genetic loci associated with plasma testosterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels have been identified using GWASs. However, GWASs have not identified any relevant loci for plasma inhibin B levels. We conducted a two-stage GWAS using 811 Japanese men in a discovery stage followed by a replication stage using an additional 721 Japanese men. The results of the discovery and replication stages were combined into a meta-analysis. After setting a suggestive significance threshold for P values < 5 × 10 -6 　in the discovery stage, we identified ten regions with SNPs (semen volume: one, sperm concentration: three, testes size: two, and inhibin B: four). We selected only the most significant SNP in each region for replication genotyping. Combined discovery and replication results in the meta-analysis showed that the locus 12q21.31 associated with plasma inhibin B levels (rs11116724) had the most significant association (P = 5.7 × 10 -8 ). The LRRIQ1 and TSPAN19 genes are located in the 12q21.31 region. This study provides new susceptibility variants that contribute to plasma inhibin B levels.

Background: CYP2A6 is an enzyme involved in oxidation of a number of environmental chemicals, including nicotine, pro-carcinogenic nitrosamines and polycyclic aromatic hydrocarbons (PAHs). The whole gene deletion of CYP2A6 (CYP2A6*4) is prevalent in East Asian population. Whether or not CYP2A6*4 associates with cancer is still controversial., Methods: We undertook an association study to determine whether deletion of CYP2A6 gene associates with total cancer and major cancer types employing data of consecutive autopsy cases registered in the Japanese single-nucleotide polymorphisms for geriatric research (JG-SNP) database. The presence of cancer were inspected at the time of autopsy and pathologically confirmed. Genotyping for CYP2A6 wild type (W) and deletion (D) was done by allele specific RT-PCR method., Results: Among 1373 subjects, 826 subjects (60.2%) were cancer positive and 547 subjects (39.8%) were cancer negative. The genotype frequency in the whole study group for WW, WD and DD were 65.0, 30.6 and 4.4%, respectively, which obeyed the Hardy-Weinberg equilibrium (p = 0.20). Total cancer presence, as well as major cancers including gastric, lung, colorectal, and blood cancers did not show any positive association with CYP2A6 deletion. When male and female were separately analyzed, CYP2A6 deletion associated with decreased gastric cancer risk in female (OR = 0.49, 95%CI: 0.25-0.95, p = 0.021, after adjustment for age, smoking and drinking). When smoker and non-smoker were separately analyzed, CYP2A6 deletion associated with decreased total cancer in female nonsmokers (OR = 0.67, 95%CI: 0.45-0.99, p = 0.041 after adjustment). On the other hand, CYP2A6 deletion associated increase blood cancers in smokers (OR = 2.05, 95%CI: 1.19-3.53, p = 0.01 after adjustment)., Conclusion: The CYP2A6 deletion may not grossly affect total cancer. It may associate with individual cancers in sex and smoking dependent manner. Further studies with larger sample size are warranted to confirm our results.

Background: A voided volume (VV) of <50% of the expected bladder capacity for age is considered small VV. It was recommended that a VV ≥50% of expected bladder capacity for age is required to assess uroflowmetry (UFM) curves because a small VV causes changes in UFM curve characteristics. However, no clear consensus has been reached on the criterion for evaluating UFM curve patterns., Objective: The aim of the study was to evaluate the reproducibility and characteristics of UFM curve patterns in children with daytime urinary incontinence (DUI) and with a variety of VVs., Methods: This study investigated 119 children (79 boys and 40 girls) with primary DUI who underwent UFM 3 times on the same day and were classified into two groups: small VV (<50% of expected bladder capacity for age) in 0-1 of the 3 UFM measurements (group 1; normal VV) or in 2-3 of the 3 UFM measurements (group 2; small VV). The authors then evaluated the agreement of UFM curve patterns among the 3 measurements, classifying complete, partial, or no agreement according to the number of identical curve patterns. The authors also evaluated the most characteristic patterns of UFM curve patterns for each group., Results: Group 1 comprised 45 children, and group 2 comprised 74 children. Rates of complete agreement (group 1, 24/45; group 2, 30/74), partial agreement (group 1, 19/45; group 2, 35/74), and no agreement (group 1, 2/45; group 2, 9/74) did not differ significantly between groups (p = 0.226). Bell curve patterns were significantly more common in group 1 than in group 2 (p = 0.025). Frequency of the tower pattern was significantly higher in group 2 than in group 1 (p = 0.006) (Summary table)., Discussion: No differences in agreement rates of UFM curve patterns were seen between two groups (small and normal VV). The authors thus suggest that UFM curve patterns can be validly assessed in children with DUI and with small VV. It was found that the bell pattern was significantly more common among children with normal VV, whereas the tower pattern was significantly more common among children with small VV. The tower pattern reflects an overactive bladder. The present results suggest that some children have DUI that is not attributable to urgency., Conclusion: Reproducibility of UFM curve patterns might be properly assessed even in children with DUI and with small VV. This result suggests the presence of various pathological conditions other than the conditions with urgency underlying DUI., (Copyright © 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: The association between stroke and nutrition has recently been investigated. However, the association between diet and stroke in Japan has not been clarified. We hypothesized that there may be an association between consumption of ramen and stroke mortality. Therefore, we investigated the association between the prevalence of ramen restaurants and stroke mortality in Japanese prefectures., Methods: We used Pearson's correlation coefficients to evaluate associations between the prevalence of each of four restaurant types (ramen, fast food, French or Italian, and udon or soba) and age- and sex-adjusted stroke mortality rates in each prefecture. We also investigated correlations between acute myocardial infarction and the prevalence of each type of restaurant as a control. We obtained age- and sex-adjusted stroke mortality rates and the acute myocardial infarction mortality rate in each prefecture from the 2017 Trends in National Health published in Japan. Data on the number of restaurants of each type in each prefecture were obtained from the database of the Nippon Telegraph and Telephone Corporation., Results: The prevalence of ramen restaurants, but not of other restaurant types, positively correlated with stroke mortality in both men and women (r > 0.5). We found no correlation between ramen restaurant prevalence and mortality from acute myocardial infarction., Conclusion: The prevalence of ramen restaurants in Japanese prefectures has a significant correlation with the stroke mortality rate.

Objective: Left ventricular free wall rupture is a catastrophic complication of acute myocardial infarction. Sutureless repair has been reported to be an effective surgical procedure for left ventricular free wall rupture. However, the outcomes of sutureless repair remain unclear., Methods: Between January 2001 and December 2016, 42 patients were treated for left ventricular free wall rupture at Jichi Medical University. Of them, 35 consecutive patients undergoing sutureless repair using the TachoComb (CSL Behring, Tokyo, Japan) or TachoSil (Nycomed, Zurich, Switzerland) patches were included in this study. No patient required cardiopulmonary bypass. The oozing type of left ventricular free wall rupture was observed in 33 patients (94%), and the blow-out type was observed in 2 patients (6%). The rupture sites were the anterior wall in 16 patients (46%), the posterior-lateral wall in 11 patients (31%), and the inferior wall in 8 patients (23%)., Results: The in-hospital mortality rate was 17% (6 patients). Re-rupture after sutureless repair occurred in 17% (6 patients). Of them, 4 cases (67%) of re-rupture occurred within 24 hours after surgery. The 2 patients with blow-out type left ventricular free wall rupture experienced re-rupture. Three patients required mitral valve surgery after sutureless repair during the admission. The overall survivals at 1, 5, and 10 years were 71.4%, 68.6%, and 62.9%, respectively. Multivariable analysis revealed that re-rupture was an independent predictor for decreased survival (hazard ratio, 58.6; 95% confidence interval, 4.9-701.6; P = .001). Postoperative pseudoaneurysm formation was not detected during the follow-up., Conclusions: Sutureless repair using TachoComb/TachoSil patches can be a viable treatment option for left ventricular free wall rupture. Care should be taken when applying this technique in cases of the blow-out type left ventricular free wall rupture., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Sarcopenia, age-related loss of muscle mass, is an objective and comprehensive marker of frailty. We aimed to clarify the influence of sarcopenia on the outcomes after heart valve surgery., Methods: We retrospectively reviewed 1119 patients who underwent valve surgery via median sternotomy at our institution from June 2009 to December 2013. Patients aged <70 years, urgent/emergent cases, and patients without preoperative computed tomography of the abdomen were excluded. The remaining 428 patients were included in this study. Psoas muscle area, a validated measure of sarcopenia, was measured on preoperative computed tomography. Sarcopenia was defined as the lowest sex-specific quartile in psoas muscle area. The mean follow-up period was 3.4 years., Results: Overall in-hospital mortality did not differ between the sarcopenia and nonsarcopenia patient groups. However, the incidence of stroke and intra-aortic balloon pump/percutaneous cardiopulmonary support use was greater in the sarcopenia group than in the nonsarcopenia group. The patients with sarcopenia had significantly decreased long-term survival and decreased freedom from major adverse cardiac and cerebrovascular events. Multivariable analysis and inverse probability weighting revealed that sarcopenia was an independent predictor for decreased survival (hazard ratio, 2.22; 95% confidence interval, 1.26-3.92; P = .006)., Conclusions: Preoperative sarcopenia defined from the psoas muscle area was associated with long-term outcomes after valve surgery. Thus, the measurement of psoas muscle area can help facilitate more accurate risk scoring in elderly patients., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Little is known concerning the prognostic significance of the degree of lymphatic vessel invasion in pancreatic head cancer. To address this gap in knowledge, we retrospectively examined 60 patients with locally advanced, surgically resectable pancreatic head cancer who underwent pancreaticoduodenectomy and lymph node (LN) dissection.All cases were histopathologically diagnosed as ductal adenocarcinoma, stage II (25 pT3N0 cases, 35 pT3N1 cases). The following variables were investigated: age; sex; neoadjuvant therapy; adjuvant therapy; tumor size; tumor grade; invasion into the serosa, retropancreatic tissue, duodenum, bile duct, portal venous system and perineural area; cut margins; LN metastasis; and the number of invaded lymphatic vessels (LVI-score).Univariate analysis demonstrated that LN metastasis and an LVI-score ≥5 were significantly associated with poor disease-free survival. Multivariate Cox regression analysis confirmed that LN metastasis and an LVI-score ≥7 were significantly associated with poor disease-free survival. Additionally, LVI-scores ≥9 and ≥10 were comparable to or surpassed the significance of LN metastasis based on the hazard ratio. Univariate analysis demonstrated that tumor size >30 mm, duodenal invasion, LN metastasis and an LVI-score ≥2 were significantly associated with poor overall survival. Multivariate Cox regression analysis confirmed that LN metastasis and LVI-scores ≥9 and ≥10 were significantly associated with poor overall survival, and an LVI-score ≥10 was comparable to or surpassed the significance of LN metastasis based on the hazard ratio.Our study strongly suggests that a high degree of lymphatic vessel invasion is associated with a poor prognosis in patients with locally advanced, surgically resectable pancreatic head cancer.

Background: Extensive data have been accumulated for adults who have undergone ABO-incompatible (ABOi)-living kidney transplantation (LKT). In contrast, available published data on pediatric recipients who underwent ABOi-LKT from the early to middle 2000s is very limited. Thus, pediatric ABOi-LKT has remained relatively rare, and there is a lack of large, multicenter data., Methods: We analyzed data from the Japanese Kidney Transplant Registry to clarify the patient and graft outcomes of pediatric recipients who underwent ABOi-LKT from 2002 to 2015. A total of 102 ABOi and 788 ABO-compatible (ABOc) recipients were identified in this study. All recipients had received basiliximab and a triple immunosuppressive protocol comprising calcineurin inhibitors, mycophenolate mofetil, and steroids. The ABOi recipients also received preconditioning therapies including B-cell depletion by a splenectomy or rituximab treatment and therapeutic apheresis., Results: Death rates for ABOi and ABOc recipients were 0.17 versus 0.17 deaths per 100 patient-years. Graft loss rates for ABOi and ABOc recipients were 1.58 versus 1.45 events per 100 patient-years. No particular causes of death or graft loss predominantly affected ABOi or ABOc recipients., Conclusions: The results of this registry analysis suggest that pediatric ABOi-LKT can be performed efficiently. Although further studies are clearly required to perform pediatric ABOi-LKT more safely and less invasively, ABOi-LKT is now an acceptable treatment for pediatric patients with end-stage renal disease.

Background: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a primary pancreatic ductal epithelial neoplasm with the potential to develop into an invasive adenocarcinoma. This study aimed to investigate the clinicopathologic and prognostic significance of four potential biomarkers for the preoperative evaluation of patients with IPMN., Materials and Methods: Clinicopathologic materials from 104 patients with IPMN who underwent surgical resection at Jichi Medical University Hospital were analyzed. IPMNs (110 lesions in total) were histologically classified into low-grade IPMN (Group 1; n = 68), high-grade IPMN (Group 2; n = 16), or IPMN with an associated invasive carcinoma (Group 3; n = 26). We evaluated the immunohistochemical expression of MUC13, AGR2, FUT8, and FXYD3, which were previously reported to be overexpressed in pancreatic ductal adenocarcinoma., Results: The expression of MUC13 was more common in Group 3 compared with groups 1 and 2 (p < 0.001) and was associated with poor prognosis (p = 0.004). The expression of MUC13 was not associated with age, sex, tumor location, histological subtype, lymphatic or vascular invasion, or neural invasion. In most cases of IPMN, the loss of expression of AGR2 appeared to show an association with tumor recurrence and poorly differentiated histology of invasive carcinoma; however, this association was not statistically significant. The expressions of FUT8 and FXYD3were not associated with the clinicopathological features of IPMNs., Conclusions: The results suggest that MUC13 overexpression and loss of expression of AGR2 may predict the progression of IPMN and an unfavorable prognosis in patients with IPMN., (Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objectives: Universal prophylaxis and preemptive therapy are used to prevent cytomegalovirus (CMV) disease post-transplantation. Data regarding which strategy is superior are sparse, especially in high-risk recipients (donor CMV seropositive (D+) and recipient CMV seronegative (R-))., Methods: This retrospective, single-center cohort study included recipients who underwent kidney transplantation between 2009 and 2015. The incidence of CMV infection/disease and patient and graft outcomes were analyzed and compared between high-risk recipients (D+/R-) and intermediate-risk recipients (D+/R+ or D-/R+), all managed with preemptive therapy., Results: Of 118 kidney transplant recipients, 21 were high-risk and 97 were intermediate-risk. Over a median follow-up period of 3 years, asymptomatic CMV infection developed significantly more frequently in high-risk patients than in intermediate-risk patients (38.1% vs. 16.5%, p=0.04), and CMV disease developed in a similar manner (28.6% vs. 3.1%, p<0.01). Among high-risk patients, CMV infection developed within the first 3 months post-transplantation and CMV disease within the first 9 months post-transplantation. Kaplan-Meier analysis showed no difference in the probability of mortality (log-rank p=0.63) or graft loss (log-rank p=0.50) between the patient groups. Graft rejection occurred more frequently in high-risk than in intermediate-risk patients, but the difference was not significant (log-rank p=0.24)., Conclusions: These results suggest that further studies on universal prophylaxis in high-risk patients are needed to elucidate whether preventing CMV infection/disease during the early post-transplant period leads to better outcomes, especially in terms of reducing graft rejection., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives　The Patient Survey provides basic information on disease and injury statistics of patients in Japan, and an estimation of the number of patients by disease and injury can be made using this survey. In this survey, the number of outpatients with repeat visits affects the survey results. The average interval since last visit (AILV) and a correction factor are used to estimate the number of repeat outpatients. Patients with AILV > 30 days are not included in the survey. However, in the last years, AILV exceeded 30 days in many cases, suggesting that the current 30-day threshold is no longer suitable. Thus, this study investigated the AILV in the current patient population and the effect of the increase in AILV on the number of repeat outpatients.Methods　Patients Survey data of 1996-2011 were used to estimate the effect of changing the AILV threshold on the number of repeat outpatients.Results　AILV increased for patients with most diseases and injuries. Using the current 30-day threshold, the overall outpatient coverage rate decreased from 91% in 1996 to 78% in 2011. A higher AILV threshold was necessary to maintain the overall outpatient coverage rate. For example, a threshold of 90 days increased the coverage rate in 2011 to 96%. However, raising the threshold markedly increased the number of repeat outpatients. For example, the overall number of repeat outpatients in 2011 increased from 43.01 million with the current 30-day threshold to 71.03 million using the 90-day threshold. The peak of the AILV of outpatients was observed on the next day after the first visit and the peak of the AILV of outpatients was observed every other week.Conclusion　AILV increased over time and changing the AILV threshold markedly increased the number of repeat outpatients and total patients, indicating that there is a need to raise the AILV threshold.

Background and Objectives: This study aimed to investigate the effects of tomato juice consumption on seminal plasma lycopene levels and sperm parameters in infertile men., Methods and Study Design: Subjects were male infertility patients with poor sperm concentration (<20×10 6/mL) and/or motility (<50%). Following a fourweek observation period, subjects were randomly assigned among three groups: a tomato juice group, an antioxidant group, and a control group. The subjects in the tomato juice group and the antioxidant group daily consumed one can of tomato juice (containing 30 mg of lycopene) or one antioxidant capsule (containing vitamin C 600 mg, vitamin E 200 mg, and glutathione 300 mg), respectively, for 12 weeks (feeding period). Seminal plasma lycopene levels and sperm parameters were measured every 6 weeks during the feeding period., Results: Forty-four patients completed the study (control group: 12, antioxidant group: 15, tomato juice group: 17). In the tomato juice group, plasma lycopene level was significantly increased at the 12th week of the feeding period. Moreover, a decrease in seminal plasma white blood cells and an increase in sperm motility in the tomato juice group were statistically significant at the 12th and 6th weeks, respectively, compared to the control group. In the antioxidant capsule group, no significant improvement was observed in semen parameters., Conclusions: In conclusion, regular consumption of tomato juice seems to improve sperm motility in infertile patients. This is the first report to show that commercially available food, such as tomato juice, might be beneficial for male infertility.

Background: Abdominal aortic aneurysm (AAA) is a multifactorial disease with strong genetic components. Various genetic loci have been associated with clinical AAA, but few studies have investigated pathological AAA, an intermediate phenotype of the disease., Methods: We examined 2263 consecutive autopsies of older Japanese subjects from a study on geriatric diseases in Japanese individuals (The JG-SNP study). The presence of AAA was determined with a pathological diagnosis during autopsy. Single nucleotide variants (SNVs) associated with AAA were determined with an Illumina HumanExome Beadchip array. Logistic regression analyses were performed to determine genetic associations. Age, gender, and other risk factors of AAA were analyzed as covariates., Results: 118 subjects with AAA and 2145 subjects without AAA were analyzed in a case-control setting. No variants reached significance after applying the Bonferroni correction ( P < 2.05×10 -6 ). The strongest associations were found with rs3750092 (p.E321G, OR: 0.36, 95% CI: 0.24-0.56, P = 6.09 × 10 -6 ), a variant in the WAS/WASL interacting protein family 3 ( WIPF3 ), and with rs1051338 (p.T16P, OR: 2.50, 95% CI: 1.70-3.66, P = 2.79 × 10 -6 ) and rs2246942 (intronic, OR: 2.32, 95% CI: 1.58-3.41, P = 1.61 × 10 -5 ), variants in the lysosomal acid lipase A ( LIPA ). LIPA is essential for macrophage cholesterol metabolism. Immunohistological analyses of WIPF3 protein in AAA samples from three subjects revealed that WIPF3 was expressed in macrophages of atheromatous plaques., Conclusions: This study suggests that WIPF3 and LIPA , both of which are expressed in the macrophages are involved in pathological AAA. These results should be regarded as hypothesis-generating; thus, replication study is warranted.

A genetic risk score (GRS) was developed for predicting fracture risk based on lifetime prevalence of femoral fractures in 924 consecutive autopsies of Japanese males. A total of 922 non-synonymous single nucleotide polymorphisms (SNPs) located in 62 osteoporosis susceptibility genes were genotyped and evaluated for their association with the prevalence of femoral fracture in autopsy cases. GRS values were calculated as the sum of risk allele counts (unweighted GRS) or the sum of weighted scores estimated from logistic regression coefficients (weighted GRS). Five SNPs (α-ʟ-iduronidase rs3755955, C7orf58 rs190543052, homeobox C4 rs75256744, G patch domain-containing gene 1 rs2287679, and Werner syndrome rs2230009) showed a significant association (P < 0.05) with the prevalence of femoral fracture in 924 male subjects. Both the unweighted and weighted GRS adequately predicted fracture prevalence; areas under receiver-operating characteristic curves were 0.750 [95 % confidence interval (CI) 0.660-0.840] and 0.770 (95 % CI 0.681-0.859), respectively. Multiple logistic regression analysis revealed that the odds ratio (OR) for the association between fracture prevalence and unweighted GRS ≥3 (n = 124) was 8.39 (95 % CI 4.22-16.69, P < 0.001) relative to a score <3 (n = 797). Likewise, the OR for a weighted GRS of 6-15 (n = 135) was 7.73 (95 % CI 3.89-15.36, P < 0.001) relative to scores of 0-5 (n = 786). The GRS based on risk allele profiles of the five SNPs could help identify at-risk individuals and enable implementation of preventive measures for femoral fracture.

Background: Our recent study showed that a low lipoproteinemia(a) [Lp(a)] level was a risk factor for cancer and all-cause deaths. The purpose of this study was to verify the role of the Lp(a) level on cancer among consecutive autopsy cases., Methods: The subjects consisted of 1354 cases (775 men and 579 women). The average age at death was 79.9 years. Hypolipoproteinemia(a) was defined as an Lp(a) level of below 80 mg/L. Overall, 62.3% of the subjects had suffered from at least one to a maximum of five malignancies throughout their lives. The most frequent type of malignancy was gastric cancer, followed by leukemia, lung cancer, and colon cancer., Results: The cancer-bearing status decreased linearly according to the Lp(a) level in both men and women (P=0.01 and P<0.001, respectively). The median Lp(a) level was significantly lower among the cases with hepato-biliary-pancreatic cancers or hematopoietic malignancy, but was higher among cases with lung cancer, especially lung adenocarcinoma. Hypolipoproteinemia(a) was a significant risk factor for any origins of cancer, with an odds ratio of 1.94 (95% CI, 1.45-2.60; P<0.001). It was also a risk factor for hepato-biliary cancers and leukemia, but it was a protective factor for lung cancer., Conclusions: Our findings suggested hypolipoproteinemia(a) would be a significant risk factor for cancer except lung cancer. This study complements our previous study showing that hypolipoproteinemia(a) would increase the lifetime risk of cancer other than lung cancer., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Although radiotherapy is recognized as an established risk factor for second malignant neoplasms (SMNs), the dose response of SMNs following radiotherapy has not been well characterized. In our previous meta-analysis of the risks of SMNs occurring among children who have received radiotherapy, the small number of eligible studies precluded a detailed evaluation. Therefore, to increase the number of eligible studies, we developed a method of calculating excess relative risk (ERR) per Gy estimates from studies for which the relative risk estimates for several dose categories were available. Comparing the calculated ERR with that described in several original papers validated the proposed method. This enabled us to increase the number of studies, which we used to conduct a meta-analysis. The overall ERR per Gy estimate of radiotherapy over 26 relevant studies was 0.60 (95%CI: 0.30-1.20), which is smaller than the corresponding estimate for atomic bomb survivors exposed to radiation as young children (1.7; 95% CI: 1.1-2.5). A significant decrease in ERR per Gy with increase in age at exposure (0.85 times per annual increase) was observed in the meta-regression. Heterogeneity was suggested by Cochran's Q statistic (P < 0.001), which may be partly accounted for by age at exposure., (© The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)