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Spontaneous intracerebral hemorrhage (SICH) remains a devastating form of stroke. Prior use of antiplatelets or warfarin before SICH is associated with poor outcomes, but the effects of direct oral anticoagulants (DOACs) remain unclear. This study aimed to clarify trends in prior antithrombotic use and to assess the associations between prior use of antithrombotics and in-hospital mortality using a multicenter prospective registry in Japan. In total, 1085 patients were analyzed. Prior antithrombotic medication included antiplatelets in 14.2%, oral anticoagulants in 8.1%, and both in 1.8%. Prior warfarin use was significantly associated with in-hospital mortality (odds ratio [OR] 5.50, 95% confidence interval [CI] 1.30–23.26, P < 0.05) compared to no prior antithrombotic use. No such association was evident between prior DOAC use and no prior antithrombotic use (OR 1.34, 95% CI 0.44–4.05, P = 0.606). Concomitant use of antiplatelets and warfarin further increased the in-hospital mortality rate (37.5%) compared to warfarin alone (17.2%), but no such association was found for antiplatelets plus DOACs (8.3%) compared to DOACs alone (11.9%). Prior use of warfarin remains an independent risk factor for in-hospital mortality after SICH in the era of DOACs. Further strategies are warranted to reduce SICH among patients receiving oral anticoagulants and to prevent serious outcomes. [ABSTRACT FROM AUTHOR]

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. Plain Language Summary: With many biologic options available for the treatment of psoriasis, choosing the optimal drug can be challenging, especially when switching drugs. Tumor necrosis factor (TNF) inhibitors are the oldest category of biologics used for psoriasis, with adalimumab and infliximab being available since 2010 and certolizumab pegol since 2019 in Japan. In this study, we examined the drug survival of TNF inhibitors in patients 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. No significant differences were noted in drug survival between the three TNF inhibitors, and the 10-year drug survival rate for adalimumab and infliximab was 14% and 18%, respectively. We examined the drug survival of subsequent biologics used by patients who discontinued TNF inhibitors for any reason (n = 137) and found that among patients who discontinued TNF inhibitors due to inadequate efficacy, female sex was a predictor of drug discontinuation and that taking interleukin-17 inhibitors rather than TNF inhibitors was a predictor of drug continuation. The study results suggest that interleukin-17 inhibitors is a favorable option for patients who discontinue TNF inhibitors due to inadequate efficacy and need to switch to other agents. However, this study has limitations, including the small number of cases and the single-center and retrospective study design. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES The incidence rate of distal stent graft-induced new entry (d-SINE) after frozen elephant trunk technique for aortic dissection remains controversial. The aim of this study was to investigate the incidence and seek the clinical and anatomical predictive factors. METHODS This study is a retrospective multicentre evaluation of complications including d-SINE, aortic events and reintervention after the frozen elephant trunk procedure for aortic dissection. RESULTS Our cohort included a total of 177 consecutive patients who underwent the frozen elephant trunk procedure for acute and chronic aortic dissection at 5 centres in Japan from May 2014 to March 2021. The incidence rate of d-SINE was 14.1% (25/177 patients). The cumulative incidence of d-SINE was 7.1%, 12.4% and 21.4% after 12, 36 and 60 months, respectively. d-SINE was not associated with mid-term survival rate. After competing risk regression analysis, onset time >48 h (subdistribution hazard ratio, 3.80; 95% confidence interval, 1.13–12.79; P  =   0.031) was detected as an independent predictor. CONCLUSIONS Awareness that there is a relatively higher incidence of d-SINE after frozen elephant trunk procedures is important. Non-hyper-acute phase was detected as an independent risk factor. Pre-emptive endovascular repair may be appropriate to protect new entry in high-risk patients. [ABSTRACT FROM AUTHOR]

Context: Few instruments in Japanese assess health-related quality of life in pediatric cancer patients.Objectives: To translate the Memorial Symptom Assessment Scale (MSAS) into Japanese pediatric and proxy versions (MSAS-J 7-12, MSAS-J 13-18, and MSAS-J-Proxy) and assess validity and reliability.Methods: Phase I comprised forward-backward translation and pilot testing in 13 children and 16 guardians. Phase II consisted of psychometric testing of the three MSAS-J versions in 162 children and 238 guardians. Internal consistency, test-retest reliability, and construct and known-group validity of the MSAS-J were assessed.Results: Cronbach's alpha coefficients for the total and subscale scores were over 0.70, excluding the psychological symptom (PSYCH) subscale score of the MSAS-J 7-12. Most MSAS-J scores significantly inversely correlated with two versions of the Pediatric Quality of Life Inventory. A strong child-guardian correlation was shown in the total and subscale scores (ICC range 0.66-0.83). Kappa estimates showed acceptable child-guardian symptom agreement. MSAS-J 7-12 and proxy differentiated patients according to clinical status.Conclusion: MSAS-J is a reliable and valid instrument to assess symptoms among Japanese children with cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: To increase the influenza vaccination rate in Chiburijima Island, we diversified vaccination places from a single clinic to the seven town halls from all the districts. Methods: We retrospectively analyzed influenza vaccination coverage, vaccinees' district of residence, and location of vaccination place, from prevaccination screening questionnaires between October 2007 and March 2018. Except for home‐visiting vaccination services, before 2011, influenza vaccination was provided only at a single clinic; after 2012, it was provided at the seven town halls in addition to the clinic. We calculated the vaccination rates among residents of Chiburijima Island, stratified by age groups and districts of residence. Results: Estimated influenza vaccination rates for all ages increased from 38% in 2007 to 58% in 2017. There was a 14% increase in coverage in 2010 (the year following the 2009 H1N1 pandemic) and a slight increasing trend after 2012. The vaccination coverage of residents, particularly of people ≥65 years old and living >1 km from the former vaccination place, increased after diversification of the vaccination place. Conclusions: Influenza vaccination rate in Chiburijima Island increased by 20% between 2007 and 2017, although the rate among the elderly Japanese people decreased by 4% based on the national data of routine immunization. Shortening the distance to vaccination places might improve the coverage as elderly people are often restricted due to transportation means. Sustained and multifaceted strategies are necessary for better immunization coverage. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Surfactant protein D (SFTPD) is a lung-specific anti-inflammatory factor that antagonizes inflammation by inhibiting oxidative stress and stimulating innate immunity. Variations in SFTPA2 and SFTPB, genes for other surfactant proteins, have been associated with lung cancer. We therefore investigated associations between SFTPD variations and lung cancer as well as emphysema and interstitial pneumonia, which are characterized by chronic inflammation from which lung cancer often arises. DNA from 1342 autopsy samples, including those from 140 subjects with lung cancer, was investigated. The single nucleotide polymorphism (SNP) rs721917, which results in methionine being exchanged for threonine at amino acid 11 (the Met11Thr variation), tended to be associated with emphysema and was associated with interstitial pneumonia and lung cancer. A haplotype analysis revealed that the haplotypes associated with emphysema and lung cancer differed from that associated with interstitial pneumonia, suggesting a differential role for SFTPD in the development of these diseases. A mediating analysis did not reveal a mediating effect exerted by emphysema or interstitial pneumonia on lung cancer. Our results suggested that SFTPD plays a role in the development of lung cancer and that the role for lung cancer may differ from that for interstitial pneumonia. [ABSTRACT FROM AUTHOR]

Incomplete Kawasaki disease (KD) is associated with delayed diagnosis and treatment, which in turn can lead to the development of coronary artery lesions (CALs). The aim of this study was to determine the epidemiological features of incomplete KD compared with complete KD and to identify risk factors for CALs from incomplete KD patients using data from a nationwide survey of 2007-2008 in Japan. A total of 23,263 patients were classified according to the number of principal clinical signs: 80% ( n = 18,620) had complete forms of KD, 14.2% had four principal signs, 4.6% had three signs, and 1.2% had only one or two signs. In comparison with complete KD cases, the prevalence of CAL development tended to be larger and the proportion receiving initial intravenous immunoglobulin (IVIG) treatment were significantly smaller in patients with incomplete forms. In addition, hospital attendance after 7 days of illness or later was significantly associated with CAL development in all incomplete groups (OR: 2.52 in total patients with incomplete KD, 3.26 in those with one or two principal signs, 2.94 in those with three signs, 2.35 in those with four signs). Conclusion The higher prevalence of CALs in incomplete KD reflects difficulties in diagnosis and delays in treatment. More timely diagnosis and treatment of incomplete KD patients could further prevent the development of cardiac lesions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

It has been unclear whether the prevalence of disability is higher in an area affected by natural disaster than in other areas even if more than one year has passed since the disaster. The aim of this ecological study was to examine whether the rate of increase in disability prevalence among the older population was higher in disaster-stricken areas during the 3 years after the Great East Japan Earthquake (GEJE) and tsunami. This analysis used public Long-term Care Insurance (LTCI) data covering 1570 municipalities. “Disaster areas” were considered to be the three prefectures most affected by the earthquake and tsunami: Iwate, Miyagi, and Fukushima. The outcome measure was the number of aged people (≥65 years) with LTCI disability certification. Rates of change in disability prevalence from January 2011 to January 2014 were used as the primary outcome variable, and compared by analysis of covariance between “coastal disaster areas”, “inland disaster areas” and “non-disaster areas”. The mean rate of increase in disability prevalence in coastal (14.7%) and inland (10.0%) disaster areas was higher than in non-disaster areas (6.2%) ( P < 0.001). During the 3 years after the earthquake, the increase of disability prevalence from before the GEJE continued to be higher in the disaster-stricken areas. [ABSTRACT FROM AUTHOR]

Background: Competency in the use of information science and technology (IST) is essential for medical students. This study identified learning objectives and competencies that correspond with low self-assessment related to use of IST and factors that improve such self-assessment among medical students., Methods: A questionnaire was administered to sixth-year medical students across 82 medical schools in Japan between November 2022 and February 2023., Results: Three learning objectives were identified as difficult for the students to achieve: (1) provide an overview of the regulations, laws, and guidelines related to IST in medicine; (2) discuss ethical issues, such as social disparities caused by the digital divide that may arise in the use of IST in medicine; and (3) understand IST related to medical care. Further, problem-based learning, engaging with IST beyond class, and learning approach impacted the students' acquisition of competencies related to IST. Furthermore, it was recognized that the competencies required by medical students may change over the course of an updated medical school curriculum., Conclusions: It is important for medical students to recognize the significance of learning, establishing active learning methods, and gaining experience in practically applying these competencies., (© 2024. The Author(s).)

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: 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.)

Objective We studied three types of estimated glomerular filtration rate (eGFR) equations and evaluated which type was strongly associated with comorbidities in living kidney transplantation (LKT) donors. Methods We compared the Japanese modified eGFR, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration equations (Jm-eGFR, Jm-MDRD, and Jm-CKD-EPI, respectively) for Japanese LKT donors with respect to their relationships with obesity, hypertension, diabetes, cardiovascular disease, and stroke. Results Of the 8,176 enrolled Japanese LKT donors, the eGFR calculated using Jm-CKD-EPI (eGFR/Jm-CKD-EPI) detected significant differences in 4 of 5 comorbidities between the comorbidity-positive and comorbidity-negative groups, whereas the eGFR calculated using Jm-MDRD (eGFR/Jm-MDRD) and Jm-eGFR (eGFR/Jm-eGFR) detected only 3 and 1 comorbidities, respectively. The area under the receiver operating characteristic curve of Jm-CKD-EPI was larger than those of Jm-eGFR and Jm-MDRD for all five comorbidities. Conclusion We found that the eGFR/Jm-CKD-EPI correlated better with comorbidities than the eGFR/Jm-eGFR and eGFR/Jm-MDRD in Japanese LKT donors. We recommend using the eGFR/Jm-CKD-EPI for the initial assessment of the renal function in LKT donor candidates when evaluating the presence of associated comorbidities.

Objectives: To investigate the impact of switching from tenofovir disoproxil fumarate (TDF)- to tenofovir alafenamide (TAF)-containing regimens on bone, kidney, serum lipids and body weight among Asian patients., Methods: A prospective, multicentre, observational cohort study was conducted at three centres for HIV infection in Japan during 2017-2019. HIV-infected adults previously treated with TDF-containing regimens and scheduled to switch to TAF-containing regimens were included. Bone mineral density (BMD), renal markers, lipids and weight were measured consecutively from 12 months before to 12 months after the switch., Results: Among 118 patients evaluated, the mean percentage change to spine BMD during 1 year of TAF treatment was higher than that during 1 year of TDF treatment (mean difference = 1.9%; 95% confidence interval (CI): 0.8-3.1). Urine protein and β 2 -microglobulin levels decreased significantly after the switch, while low-density lipoprotein cholesterol and triglycerides increased. During the TDF and TAF periods, the mean weight gains were 0.2 and 1.9 kg, respectively (mean difference = 1.6 kg; 95% CI: 0.9-2.3). Subgroup analysis revealed a significant difference between the mean body weight change associated with an integrase inhibitor (INSTI) (+2.8 kg) and that associated with a non-INSTI (+1.2 kg) third agent treatment only during the TAF period., Conclusions: Among predominantly Japanese HIV-infected patients, BMD and renal tubular markers improved, while lipid profiles worsened significantly after the switch. Weight gain during the TAF period was larger than that during the TDF period. Concurrent use of INSTI with TAF may act synergistically to gain body weight., (© 2021 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

The HOTAIR gene encodes a long noncoding RNA (lncRNA), which functions in development and tumorigenesis. A single nucleotide polymorphism (SNP) rs920778 in the HOTAIR gene, has been recurrently studied for susceptibility to many cancers including oesophageal cancer, gastric cancer, lung cancer, and hepatocellular carcinoma. Most of these studies were conducted in Chinese populations, and a few in Turkish, Iranian, and Portuguese populations. They mostly give rise to controversial results. It still remains largely unknown whether the cancer risk is conferred in a Japanese population. Here, we established an association study on the representative SNP rs920778, to examine its contribution to the presence of cancer in consecutive autopsy cases in the JG-SNP database. A total of 1373 subjects (mean age 80) including 827 cancer positive and 546 cancer negative subjects were analyzed. As a result, the occurrence of overall cancer was not associated with the rs920778 polymorphism (p > 0.05). For each cancer type, we did not find association except for lung cancer (p = 0.04) which was more likely a by-chance association after multiple testing. Our findings imply that rs920778 polymorphism does not affect total cancer presence and the effect on specific cancer types is also weak in the Japanese population., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This is a Japanese retrospective single-center study carried out between 1 January 2010 and 21 November 2018 at the Department of Dermatology in Jichi Medical University Hospital. The drug survival rate for six biologic agents used for the treatment of psoriasis was investigated. We reviewed the clinical records of 315 treatment series of 205 patients with moderate to severe psoriasis treated with adalimumab (103 cases), infliximab (70 cases), ustekinumab (66 cases), secukinumab (38 cases), brodalumab (12 cases) and ixekizumab (26 cases). In our study, ustekinumab revealed a trend towards higher drug survival among the six biologic agents. Ustekinumab had a higher drug survival rate than infliximab and secukinumab with significant differences by log-rank test among all patients and among biologic-naive (bio-naive) patients. There was no significant difference in drug survival between bio-naive and biologic-experienced (non-naive) patients in the treatment courses with adalimumab, infliximab, ustekinumab, secukinumab and ixekizumab. The dose augmentation therapy in infliximab-treated patients was associated with longer drug survival. Of all patients, 25 cases with generalized pustular psoriasis (GPP) were included, who functioned as the negative predictor for drug persistence with a hazard ratio of 1.87 (95% confidence interval, 1.12-3.11; P = 0.016). Our results reveal that ustekinumab had a superior drug survival, which is supported by the previous studies. Further studies are needed to clarify the efficacy of biologic agents on patients with GPP., (© 2019 Japanese Dermatological Association.)

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.)

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.)

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: Clinical characteristics and treatment outcomes of acute type A aortic dissection with D-dimer elevation have not been clarified., Methods and Results: D-dimer was measured preoperatively within 24 hours of symptom onset in 262 patients with acute type A aortic dissection. The median (and interquartile range) admission D-dimer concentration in our total patient group was 26.7 (8.3-85.9) μg/mL. Median (interquartile range) D-dimer concentrations were 5.0 (2.6-18.0) μg/mL for complete false lumen thrombosis (n=33), 60.9 (19.4-160.4) μg/mL for partial thrombosis (n=81), 26.5 (10.0-70.6) μg/mL for a patent false lumen (n=131), and 8.7 (3.2-26.9) μg/mL for ulcerlike projection (n=17) ( P< 0.01). With a D-dimer concentration of ≤8.3 μg/mL representing the lower quartile, we then investigated predictors of a low D-dimer level. Multivariate analysis showed dissection limited to the ascending aorta ( P< 0.01; odds ratio, 9.81) or descending aorta ( P< 0.01; odds ratio, 7.68), a completely thrombosed false lumen ( P< 0.01; odds ratio, 4.02), and absence of brain ischemia ( P= 0.013; odds ratio, 4.74) to be predictors of the lower D-dimer concentration. Compared with patients with a low D-dimer concentration (≤8.3 μg/mL, n=66), patients with a D-dimer concentration >8.3 μg/mL (n=196) had a reduced preoperative platelet count and increased operation time and transfusion volume. In-hospital mortality was elevated in this group (1.5% versus 11.2%; P= 0.031), although 7-year survival did not differ for hospital survivors (lower versus higher, 93.1% versus 79.1%; P =0.21)., Conclusions: D-dimer concentrations are strongly influenced by the extent of dissection and false lumen status. Operative risks are increased in patients with a relatively high D-dimer concentration., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

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.

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: The Ryanodine receptor 3 gene (RYR3) encodes an intracellular calcium channel that mediates the efflux of Ca2+ from intracellular stores. Two single-nucleotide polymorphisms (SNPs) in the RYR3 gene have been shown to associate with stroke (rs877087) and carotid intima-media thickness (rs2229116) in two independent genome-wide association studies (GWAS) in Caucasian. We investigated the effect of these two SNPs as well as the 31.1 kilobases spanning region on atherosclerosis in Japanese population., Methods: Atherosclerotic severity was assessed by carotid artery (n = 1374) and pathological atherosclerosis index (PAI) (n = 1262), which is a macroscopic examination of the luminal surfaces of 8 systemic arteries in consecutive autopsy samples. 4 tag SNPs in the 31.1 Kb region, rs877087, rs2132207, rs658750 and rs2229116, were genotyped and haplotypes were inferred to study the association with atherosclerotic indices., Results: rs877087 and rs2229116 were associated with PAI (OR = 2.07 [1.04-4.12] (95% CI), p = 0.038; and OR = 1.38 [1.02-1.86], p = 0.035, respectively). rs2229116 was also associated with common carotid atherosclerosis (OR = 1.45 [1.13-1.86], p = 0.003). The risk allele of rs2229116 was opposite from the original report. The haplotype block of this 31.1 Kb region was different between Caucasian and Japanese. Haplotype analysis revealed that only TAGG haplotype was associated with PAI (OR = 0.67 [0.48-0.94], p = 0.020) and atherosclerosis of common carotid artery (OR = 0.75 [0.58-0.98], p = 0.034)., Conclusion: rs877087 and rs2229116 of RYR3 gene are associated with atherosclerosis severity in Japanese. The functional difference caused by rs2229116 needs to be investigated.

Objectives: Acute respiratory distress syndrome is characterized by diffuse alveolar damage and increased extravascular lung water levels. However, there is no threshold extravascular lung water level that can indicate diffuse alveolar damage in lungs. We aimed to determine the threshold extravascular lung water level that discriminates between normal lungs and lungs affected with diffuse alveolar damage., Design: A retrospective analysis of normal lungs and lungs affected with diffuse alveolar damage was performed., Setting: Normal lung cases were taken from published data. Lung cases with diffuse alveolar damage were taken from a nationwide autopsy database. All cases of autopsy followed hospital deaths in Japan from more than 800 hospitals between 2004 and 2009; complete autopsies with histopathologic examinations were performed by board-certified pathologists authorized by the Japanese Society of Pathology., Patients: Normal lungs: 534; lungs with diffuse alveolar damage: 1,688., Interventions: We compared the postmortem weights of both lungs between the two groups. These lung weights were converted to extravascular lung water values using a validated equation. Finally, the extravascular lung water value that indicated diffuse alveolar damage was estimated using receiver operating characteristic analysis., Measurements and Main Results: The extravascular lung water values of the lungs showing diffuse alveolar damage were approximately two-fold higher than those of normal lungs (normal group, 7.3±2.8 mL/kg vs diffuse alveolar damage group 13.7±4.5 mL/kg; p<0.001). An extravascular lung water level of 9.8 mL/kg allowed the diagnosis of diffuse alveolar damage to be established with a sensitivity of 81.3% and a specificity of 81.2% (area under the curve, 0.90; 95% CI, 0.88-0.91). An extravascular lung water level of 14.6 mL/kg represented a 99% positive predictive value., Conclusions: This study may provide the first validated quantitative bedside diagnostic tool for diffuse alveolar damage. Extravascular lung water may allow the detection of diffuse alveolar damage and may support the clinical diagnosis of acute respiratory distress syndrome. The best extravascular lung water cut-off value to discriminate between normal lungs and lungs with diffuse alveolar damage is around 10 mL/kg.

Estrogens are thought to play an important role in bone metabolism through estrogen receptors (ER). Dinucleotide (cytosine-adenine, CA) repeat polymorphism in the human ER-β gene (ESR2) has been reported to be associated with bone mineral density. We aimed to further elucidate the importance of this polymorphism in the pathogenesis of osteoporosis by examining its association with the incidence of femoral fracture. Deoxyribonucleic acids extracted from the renal cortex of 1489 consecutive Japanese autopsies (799 male, mean age 79 years, 690 female, mean age 82 years) with complete clinical/pathological data were enrolled in the study. ESR2 CA repeat polymorphism was determined by polymerase chain reaction using fluorescein-labeled primers. The presence or absence of femoral fracture during each subject's lifetime was determined by thorough examination of the clinical record. Incidence of femoral fracture in subjects bearing at least one allele of 20 CA repeats (4/132, 3.0 %) was significantly lower than in those without this allele (127/1357, 9.4 %, P = 0.0098). After adjustments for age and sex, logistic regression analysis revealed that having no allele of 20 CA repeats was an independent risk factor of femoral fracture [adjusted odds ratio (OR) 3.875, 95 % confidence interval (CI) 1.392-10.788, P = 0.0095], which was emphasized among women (adjusted OR 6.360, 95 % CI 1.520-26.618, P = 0.0133). Japanese subjects, especially women, bearing at least one allele of 20 CA repeats in the ESR2 may have a lower risk of femoral fracture than those without it, suggesting this polymorphism plays a role in bone metabolism.

Background: Experimental studies support the anti-neoplastic effect of apo(a), but several clinical studies have reported contradictory results. The purpose of this study was to determine whether a low lipoprotein(a) [Lp(a)] concentration is related to mortality from major causes of death, especially cancer., Methods: The subjects were 10,413 participants (4,005 men and 6,408 women) from a multi-center population-based cohort study in Japan (The Jichi Medical School cohort study). The average age at registration was 55.0 years, and the median observation period was 4,559 days. As the estimated hazard ratio was high for both the low and very high Lp(a) levels, we defined two Lp(a) groups: a low Lp(a) group [Lp(a)<80 mg/L] and an intermediate-to-high Lp(a) group [Lp(a) ≥ 80]. Participants who died from malignant neoplasms (n = 316), cardiovascular disease (202), or other causes (312) during the observation period were examined., Results: Cumulative incidence plots showed higher cumulative death rates for the low Lp(a) group than for the intermediate-to-high Lp(a) group for all-cause, cancer, and miscellaneous-cause deaths (p<0.001, p = 0.03, and p = 0.03, respectively). Cox proportional hazards analyses with the sex and age of the participants, body mass index, and smoking and drinking histories as covariates showed that a low Lp(a) level was a significant risk for all-cause, cancer, and miscellaneous-cause deaths (p<0.001, p = 0.003, and p = 0.01, respectively). The hazard ratio (95% CI) [1.48, 1.15-1.92] of a low Lp(a) level for cancer deaths was almost the same as that for a male sex (1.46, 1.00-2.13)., Conclusions: This is the first report to describe the association between a low Lp(a) level and all-cause or cancer death, supporting the anti-neoplastic effect of Lp(a). Further epidemiological studies are needed to confirm the present results.

Aim: We previously reported significant associations between mitochondrial single nucleotide polymorphisms (mtSNPs) and myocardial infarction, atherothrombotic cerebral infarction, metabolic syndrome and type 2 diabetes. Here, we assessed the hypothesis that mtSNPs may confer a risk for atherosclerosis, the most important intermediate phenotype of ischemic cardiovascular events., Methods: The subjects were 1,536 consecutive autopsy cases (827 men and 709 women). The average age at death was 80 years. The severity of coronary atherosclerosis was semi-quantitatively examined on cut sections. We examined 149 mtSNPs using the PCR-Luminex method, with a success rate of 97%. Phylogenetic tree analysis yielded 36 haplogroups. Multiple logistic regression analysis was performed after adjustments for sex, age, and conventional cardiovascular risk factors., Results: Among the 45 mtSNPs with minor genotype frequencies >0.05, 6 mtSNPs were associated with coronary atherosclerosis. Among 10 haplogroups with frequencies >0.04, haplogroups A and M7a were significantly associated with coronary atherosclerosis, with odds ratios (95% confidence intervals) of 1.80 (1.09-2.97; p=0.023) and 1.92 (1.23-3.01; p=0.004), respectively. Haplogroup D4a, which was previously reported to be associated with extreme longevity in a Japanese population, was associated with pathological myocardial infarction in men with an odds ratio of 2.05 (1.01-4.14; p=0.046)., Conclusions: The mitochondrial haplogroups A and M7a confer a significant risk for coronary atherosclerosis in the Japanese. The mitochondrial haplogroup may contribute some genetic risk for coronary heart disease.