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Introduction/aims: Multifocal motor neuropathy (MMN) is a rare disease for which epidemiological and clinical data are limited. We conducted a nationwide survey to determine disease prevalence, incidence, clinical profile, and current treatment status in Japan., Methods: A nationwide survey was conducted in 2021 using an established epidemiological method. Questionnaires were sent to all neurology and pediatric neurology departments in Japan. An initial questionnaire was administered to determine the number of patients with and incidence of MMN. A second questionnaire was administered to collect detailed clinical information. The European Federation of Neurological Societies/Peripheral Nerve Society 2010 guidelines were used as diagnostic criteria., Results: The estimated number of patients with MMN was 507. The estimated prevalence was 0.40 per 100,000 individuals. Detailed clinical profiles were available for 120 patients. The male-to-female ratio was 2.3:1 and the median onset age was 42 years. The median disease duration at diagnosis was 25 months. Most patients presented with upper limb-dominant muscle weakness. Motor nerve conduction blocks were found in 62% of patients and positive anti-GM1 IgM antibody results in 54%. A total of 117 (98%) patients received immunoglobulin therapy, and 91% of them showed improvement. At the time of the last visit (median, 82 months from treatment initiation), 89 (74%) patients were receiving maintenance immunoglobulin therapy. A slight progression of neurological deficits was observed during follow-up., Discussion: Most patients with MMN in Japan received induction and maintenance immunoglobulin therapies, which appear to suppress long-term disease progression., (© 2024 Wiley Periodicals LLC.)

Pericardial effusion (PE) presentation varies from an incidental finding to a life-threatening situation; thus, its etiology and clinical course remain unknown. The aim of the present study was to retrospectively investigate these factors.We analyzed 171 patients (0.4%) who presented with PE among 34,873 patients who underwent echocardiography between 2011 and 2021 at our hospital. Clinical and prognostic information was retrieved from electronic medical records. The primary endpoints were all-cause death, hospitalization due to heart failure (HF), and other cardiovascular events such as cardiovascular death, acute coronary syndrome, elective percutaneous coronary intervention, and stroke.The etiologies of PE were as follows: idiopathic (32%), HF-related (18%), iatrogenic (11%), cardiac surgery-related (10%), radiation therapy-related (9%), malignancy (8%), pericarditis/myocarditis (8%), myocardial infarction-related (2%), and acute aortic dissection (2%). Patients with idiopathic/HF etiology were more likely to be older than the others.During a mean follow-up period of 2.5 years, all-cause death occurred in 21 patients (12.3%), cardiovascular events in 10 patients (5.8%), and hospitalization for HF in 24 patients (14.0%). All-cause death was frequently observed in patients with malignancy (44% per person-year). Cardiovascular events were mostly observed in patients with radiation therapy-related and malignancy (8.6% and 7.3% per person-year, respectively).The annual incidence of hospitalization for HF was the highest in patients with HF-related (25.1% per person-year), followed by radiation therapy-related (10.4% per person-year).This retrospective study is the first, to the best of our knowledge, to reveal the contemporary prevalence of PE, its cause, and outcome in patients who visited a cardiovascular hospital in an urban area of Japan.

Background and Purpose: The aim of this study was to determine the prevalence of anti-myelin-associated glycoprotein (MAG) neuropathy and the current status of such patients in Japan., Methods: We conducted a nationwide survey in 2021 using established epidemiological methods. Questionnaires were sent to all neurology and pediatric neurology departments throughout Japan to identify patients with anti-MAG neuropathy. An initial questionnaire was used to determine the number of patients, with a second one used to collect detailed clinical information., Results: The estimated number of patients with anti-MAG neuropathy was 353, with a prevalence of 0.28 per 100,000 and an incidence of 0.05 per 100,000. The detailed clinical profiles of 133 patients were available. The median (range) age of onset was 67 (30-87) years, with a prominent peak in the age range 66-70 years, and the male-to-female ratio was 3.6. Most patients had distal sensory-predominant polyneuropathy, and neuropathic pain (50%), or sensory ataxia (42%), while 18% had Waldenström's macroglobulinemia or multiple myeloma. Intravenous immunoglobulin was the most frequently used treatment (65%), but the response rate was <50%, whereas rituximab was given in 32% of patients, and 64% of these showed improvement. At the last visit, 27% of patients could not walk independently., Conclusions: This study on anti-MAG neuropathy provides updated insights into the epidemiology of this disease, clinical profiles, and treatment approaches in Japan. Rituximab therapy, used for only one-third of the patients, demonstrated efficacy. During the final visit, a quarter of the patients were unable to walk independently. Further studies are warranted to determine the optimal management of this rare and intractable disorder., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Objectives: To investigate the current epidemiology, clinical profile, and treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) using a nationwide survey in Japan., Methods: We conducted a nationwide survey using an epidemiologic method established in 2021. Questionnaire sheets were sent to the hospital departments of neurology and pediatric neurology throughout Japan. A primary questionnaire was used to determine the number of patients and their prevalence, and a second questionnaire was used to collect detailed clinical information., Results: The primary survey showed that the estimated number of patients with CIDP was 4,180, with a prevalence of 3.3 per 100,000 persons. In the secondary survey, detailed clinical data were available for 1,257 patients. The male-to-female ratio was 1.5:1, and the median age at onset was 52 years. Typical CIDP was the most frequent subtype (52%), followed by distal (17%) and multifocal/focal CIDP (17%). Initial treatments included immunoglobulin therapy (72%), corticosteroids (15%), and others (13%). Among patients with CIDP, 78% had a progressive/relapsing course, 14% did not respond to first-line treatments, and 18% could not walk independently at the last visit. Among the subtypes, typical CIDP had the most severe disability before treatment (44% of patients could not walk independently). However, they showed a more favorable response to treatment than those with distal or multifocal CIDP. In the subgroup analyses, logistic regression analyses showed that younger age at onset, no muscle atrophy, and abnormal median-normal sural sensory nerve responses were associated with a higher probability of independent walking., Discussion: Our study represents the largest cohort study on CIDP to demonstrate the current epidemiologic and clinical status of CIDP in Japan. Clinical subtypes seem to be associated with different treatment responses and outcomes; therefore, an appropriate treatment strategy according to the pathophysiology of each subtype is required to improve the prognosis of CIDP.

There are a limited number of studies in which the depression status was followed up throughout pregnancy and postpartum to 1 year after delivery though 8.6-33% of women with recurrent pregnancy loss (RPL) and 10-25% of women who undergo in vitro fertilization and embryo transfer (IVF-ET) suffer from depression. We examined whether RPL and IVF-ET affect depressive symptoms during pregnancy and postpartum. A nationwide large-scale birth cohort study known as the "Japan Environment and Children's Study (JECS)" was conducted. The subjects consisted of 99,202 pregnant women recruited between January 2011 and March 2014. The Kessler Psychological Distress Scale was used for the 1st trimester, 2nd/3rd trimester and 1 year postpartum. The Edinburgh Postnatal Depression Scale was used for the first and the sixth month postpartum. The screening instruments were used to quantify depressive symptoms. Women with no live births had a significantly higher prevalence of elevated depressive symptoms throughout pregnancy and postpartum. The prevalence of elevated depressive symptoms was significantly higher in the second/third trimester among women with three or more pregnancy losses with no live births. IVF-ET was associated with reduced risk of developing depressive symptoms during all pregnancies and at 1 and 6 months after delivery in women with no live births. RPL and IVF-ET did not affect postpartum depressive symptoms, and IVF-ET rather reduced the risk of depression throughout pregnancy and postpartum. Psychological support for RPL women would be necessary., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Glasgow prognostic score (GPS) has been used to evaluate inflammatory response and nutritional status. This study aimed to investigate the impact of nutritional status on cardiac prognosis by using GPS in patients after undergoing percutaneous coronary intervention (PCI). We included 862 patients who underwent PCI for stable angina pectoris between 2015 and 2018. We used the original cutoff values, which were an albumin (Alb) level of 3.5 g/dl and a C-reactive protein (CRP) level of 0.3 mg/dl. We categorized them into the three groups: originally defined GPS (od-GPS) 0 (high Alb and low CRP), 1 (low Alb or high CRP), and 2 (low Alb and high CRP). Major adverse clinical events (MACEs) included all-cause death, nonfatal myocardial infarction, revascularization, and hospitalization for heart failure. The median follow-up period was 398.5 days. During the follow-up, MACEs occurred in 136 patients. Od-GPS 2 had higher prevalence rates in terms of chronic kidney disease (CKD; 31.7% [229/722] vs. 44.9% [53/118] vs. 63.6% [14/22], p < 0.001), hemodialysis (6.4% [46/722] vs. 14.4% [17/118] vs. 31.8% [7/22], p < 0.001), and heart failure cases (HF; 9.1% [66/722] vs. 14.4% [17/118] vs. 27.3% [6/22], p = 0.007), with higher creatinine (1.17 ± 1.37 mg/dl vs. 1.89 ± 2.60 mg/dl vs. 3.49 ± 4.01 mg/dl, p < 0.001) and brain natriuretic peptide levels (104.1 ± 304.6 pg/ml vs. 242.4 ± 565.9 pg/ml vs. 668.1 ± 872.2 pg/ml, p < 0.001) and lower low-density lipoprotein cholesterol (101.5 ± 32.9 mg/dl vs. 98.2 ± 28.8 mg/dl vs. 77.1 ± 24.3 mg/dl, p = 0.002) than od-GPS 0 and 1.Od-GPS 2 (HR 2.42; 95% CI 1.16-5.02; p = 0.018), od-GPS 1 (HR 2.09; 95% CI 1.40-3.13; p < 0.001), diabetes (HR 1.41; 95% CI 1.00-1.99; p = 0.048), CKD (HR 2.10; 95% CI 1.49-2.96; p < 0.001), and HF (HR 1.64; 95% CI 1.05-2.56; p = 0.029) were independent predictors of MACEs. A scoring system using CRP and Alb levels with a milder definition than GPS suitably predicted the risk of MACEs in the patients who underwent PCI., (© 2021. Springer Japan KK, part of Springer Nature.)

Background: Longitudinal adverse effects of neglect-related behaviors during postpartum, especially repeated maternal non-responsiveness to the crying baby on their neuropsychological developmental trajectory, have not been fully clarified., Objective: This study aimed to examine the association between postpartum maternal neglect-related behaviors and infant neuropsychological outcomes using the Japan Environment and Children's Study (JECS)., Participants and Setting: JECS data on 100,286 mother-child pairs were analyzed. Explanatory variables were "frequency of leaving the baby alone at home" (i.e., leaving the baby alone at home) and "frequency of ignoring the baby when he or she cries" (i.e., ignoring the crying baby) at one month postpartum. The outcomes were measured using the Japanese version of the Ages & Stages Questionnaires-Third Edition (J-ASQ-3)., Methods: After multiple imputations, logistic regression analysis was performed to evaluate the association between neglect-related behaviors and the J-ASQ-3 domains at each age., Results: The "sometimes or more" group of "ignoring the crying baby" from six months to three years reported relatively consistent significant associations with developmental delay in communication (maximum adjusted odds ratio [aOR]: 1.456, 95% confidence interval [CI]: 1.261-1.682), gross motor (maximum aOR: 1.279, 95% CI: 1.159-1.411), fine motor (maximum aOR: 1.274, 95% CI: 1.113-1.457), problem-solving (maximum aOR: 1.178, 95% CI: 1.104-1.256), and personal-social domains (maximum aOR: 1.326, 95% CI: 1.255-1.402). The adverse effects of "leaving the baby alone at home" disappeared in many domains by the age of one., Conclusions: Repeated maternal non-responsiveness to baby's crying during postpartum may suppress multiple neuropsychological development during early childhood., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/aim: Ra-223 is a therapeutic agent for bone metastatic castration-resistant prostate cancer (mCRPC). We examined the efficacy of a treatment method using Ra-223 together with ethinylestradiol (EE)., Patients and Methods: Patients who received Ra-223 three or more times were included and two groups (with or without EE) were compared retrospectively., Results: Eighteen patients were treated with Ra-223 and EE concomitantly (EstRadium therapy) and 13 patients were treated with Ra-223 alone or Ra-223 and agents other than EE (non-EstRadium therapy). The number of patients with decreased serum prostate-specific antigen level was significantly higher in the EstRadium therapy group than in the non-EstRadium therapy group (p=0.029)., Conclusion: The combination of Ra-223 and EE, compared to Ra-223 alone, is an effective treatment option for bone mCRPC patients, in terms of PSA response., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

To discuss appropriate physical activity (PA) levels during pregnancy, this prospective cohort study examined the relationships between PA levels before and during pregnancy and physical and mental health status. Fixed data for 104,102 pregnant women were used from the Japan Environment and Children's Study, of which data for 82,919 women were analyzed after excluding women with multiple birth and pregnancy complications. PA levels were measured using the International Physical Activity Questionnaire-Short Form. The 8-Item Short Form Health Survey was used to measure outcomes. Logistic regression with multiple imputations showed that moderate PA for over 720 min/wk and vigorous PA before pregnancy were associated with poorer mental health in the first trimester (adjusted odds ratio (AOR): 1.087-1.376. Walking in the second and third trimesters was associated with better physical and mental health (AOR: 0.855-0.932). Moderate PA over 1080 min/wk and vigorous PA in the second and third trimesters were associated with poorer mental health (AOR: 1.223-1.873). Increases over 4135.4 MET-min/wk and decreases in PA levels were associated with poorer mental and physical health (AOR: 1.070-1.333). Namely, pregnant women receiving health benefits prefer continuous walking in addition to avoiding vigorous PA and excessive changes in PA levels during pregnancy.

Background/aim: Vintage hormone therapy for non-metastatic castration-resistant prostate cancer (nmCRPC) is not recommended under the current guidelines, but is widely practiced in Japan. This study assessed effectiveness of vintage hormone therapy as alternative androgen deprivation therapy (AADT) for treatment of nmCRPC., Patients and Methods: In this retrospective study we examined patients with nmCRPC that received vintage hormone therapy as AADT between 1999 and 2018., Results: Of 53 patients with nmCRPC, 25 patients (47.2%) had stage 1 nodal disease (N1) at diagnosis of nmCRPC. Prostate specific antigen (PSA) reduction rate≥30% was observed in 32 patients (72.7%). The median PSA nadir was 0.7, and the duration of the response was 14.3 months. The median metastasis-free survival (MFS) for the entire patient population was 62.2 months, and the median overall survival (OS) was not reached. In the multivariate analysis, the duration of response in AADT>18 months was a predictor of prolonged OS., Conclusion: There is a certain number of nmCRPC patients who respond well to vintage hormone therapy as AADT. Further studies are expected to differentiate such cases., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Initial screening for proteinuria by urine dipstick test (UDT) may be useful for predicting clinical outcomes. The Shinken Database includes all the new patients visiting the Cardiovascular Institute Hospital in Tokyo, Japan. Patients for whom UDT was performed at their initial visit between 2004 and 2010 (n = 7131) were divided into three groups according to the test results: negative, trace, and positive (1+ to 4+) proteinuria. During the mean follow-up period of 3.4 years, 233 (3.1%) deaths, 255 (3.6%) heart failure (HF) events, and 106 (1.5%) ischemic stroke (IS) events occurred. Prevalence of atherothrombotic risks increased with an increase in the amounts of proteinuria. The incidence of all-cause death, HF and IS events increased significantly from negative to trace to positive proteinuria groups (log rank test, P for trend < 0.001). Multivariate analysis revealed independent association between proteinuria and all-cause death [hazard ratio (HR): 1.50, 95% confidence interval (CI) 1.07-2.10], HF (HR: 1.55, 95% CI 1.14-2.12), and IS (HR: 2.08, 95% CI 1.26-3.45). Even trace proteinuria was independently associated with HF (HR: 1.64, 95% CI 1.07-2.53) and IS (HR: 2.17, 95% CI 1.14-4.11) and with all-cause death (HR: 1.56, 95% CI 0.99-2.47). In conclusions, dipstick proteinuria was independently associated with cardiovascular events and death, suggesting that the UDT is a useful tool for evaluating patients' risk for such adverse events.

Treatment and prognosis of elderly patients with atrial fibrillation (AF) may differ by the experience of fall or bone fracture. However, their current status is still unclear. From our institute database between 2010 and 2015, 674 AF patients with age ≥ 70 years were selected and were divided into those who experienced fall or fracture during the observation period (F/F group; n = 49) and those who did not (non-F/F group; n = 625). We compared the treatment and prognosis between the 2 groups. Patients in the F/F group were older (79 vs 76 years, P < 0.001) and had more comorbidities compared with those in the non-F/F group. The prescription rate of oral anticoagulant was similar between the two groups (77.6% vs 68.2%, P = 0.201), where warfarin was predominant. The F/F group was not associated with higher incidence of ischemic stroke. The F/F group was associated with a higher incidence of heart failure events (adjusted odds ratio (OR) 3.88; 95% confidence intervals (Cl) 1.70-8.85; P = 0.001), and cardiovascular events (OR 3.43; 95% Cl 1.71-6.85; P < 0.001). In elderly AF patients in a cardiovascular hospital, the experience of fall or fracture did not affect the prescription of oral anticoagulants and the incidence of ischemic stroke, but it was significantly associated with increase of heart failure.

The effects of prenatal exposure to household pesticides on fetal and neonatal growth have not been fully clarified. The present study aims to determine the effects of prenatal exposure to pesticides on neonates' body size and growth during the first month. This study included 93,718 pairs of pregnant women and their children from the Japan Environment and Children's Study. Participants completed self-reporting questionnaires during their second or third trimesters on their demographic characteristics and frequency of pesticide use during pregnancy. Child weight, length, and sex were obtained from medical record transcripts. Birth weight and length, as well as weight and length changes over the first month, were estimated using an analysis of covariance. Frequency of exposure to almost all pesticides had no effects on birth weight and length. However, we found small but significant associations (i) between the use of fumigation insecticides and decreased birth weight, and (ii) between frequencies of exposure to pyrethroid pesticides, especially mosquito coils/mats, and suppression of neonatal length growth. Prenatal exposure to household pesticides, especially those containing pyrethroids, might adversely influence fetal and postnatal growth trajectories.

In Japanese surveillance in an early phase after the approval of rivaroxaban, inappropriate underdose was frequently utilized. The aim of this study was to describe the prevalence and predictors of the inappropriate usage of rivaroxaban in a single-center, cardiovascular-specialized hospital. Consecutive 661 non-valvular atrial fibrillation (NVAF) patients treated with rivaroxaban between 2012 and 2017 were recruited. After excluding 30 patients without assessment of creatinine clearance (CCr), the proportion and predictors of inappropriate underdose were analyzed. Additionally, patient outcomes, including thromboembolism (ischemic stroke or systemic embolism) and major bleeding, were determined. In patients with CCr ≥ 50 mL/min (n = 532) and < 50 mL/min (n = 98), inappropriate underdose and overdose were used in 123 (23%) and 8 (8%), respectively. The predictors of inappropriate underdose (in patients with CCr ≥ 50 mL/min) were CCr [50-63 mL/min (the lowest tertile) compared to ≥ 64 mL/min], age ( ≥ 75 years), female gender, prescription of antiplatelet, and coexistence of heart failure. Although PT under rivaroxaban was lower in patients with inappropriate underdose than in those with an appropriate dose, no significant increase in the incidence of thromboembolism or major bleeding was observed within the mean follow-up of 683 days. Inappropriate underdose of rivaroxaban was frequently observed for NVAF patents even in a cardiovascular hospital, particularly in patients with CCr adjacent to the dose reduction criteria. The responses of PT and the incidence of adverse outcomes under an inappropriate dose of rivaroxaban should be further investigated.

Objectives: Several studies have suggested a possible relationship between atrial fibrillation (AF) and falls. However, whether the relationship depends on AF types is unclear. We investigated the relationship between sustaining AF and falls., Design: Single hospital-based cohort study with a follow-up of falls within 3 years after baseline., Setting and Participants: A total of 14,056 patients from our cohort between February 2010 and March 2016., Measures: Incidence of falls within 3 years by baseline cardiac rhythm was measured, and we investigated the effects of AF types on incidence of falls., Results: The study population was divided into younger (<75 years old; n = 11,808) and older (≥75 years old; n = 2248) groups, and then divided into 3 groups according to the baseline cardiac rhythm: sinus rhythm (SR), paroxysmal AF (PAF), and persistent AF (PeAF). There were more male patients in the PeAF group; these patients had more comorbidities both in the younger and older groups. The cumulative incidence rates of falls at 1 year in patients with SR, PAF, and PeAF were similar in the younger group (0.4%, 0.4%, and 0.6%, respectively; P = .496), whereas those were significantly different in the older group (2.3%, 2.7%, and 5.0%, respectively; P = .024). In multivariate analysis, both PAF [hazard ratio (HR) 1.179; 95% confidence interval (CI) 0.553-2.511, reference SR] and PeAF (HR 1.502; 95% CI 0.635-3.556) were not associated with falls in the younger group. In the older group, PeAF was independently associated with incidence of falls (HR 2.257; 95% CI 1.262-4.037), but PAF was not (HR 1.317; 95% CI 0.673-2.574)., Conclusions/implications: PeAF, not PAF, was associated independently with falls in older patients, suggesting the possible effect of irregular beats on physical frailty in the older population., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background:  Since venous thromboembolism (VTE) is one of the causes of maternal mortality, several guidelines recommend prophylaxis using low molecular weight heparin for women in high-risk groups. The number of large population-based studies examining predictors for VTE has been limited, and there has been no study based on a Japanese population., Objective:  Our objective was to examine VTE risk factor during the pregnancy and post-partum period., Materials and Methods:  A nationwide birth cohort study known as the 'Japan Environment and Children's Study (JECS)' was conducted by the Ministry of the Environment. The subjects consisted of 103,070 pregnancies recruited by the JECS between January 2011 and March 2014. Pregnant women completed the questionnaires during the first and second/third trimester. Their medical records were transcribed by physicians or research coordinators at registration, just after delivery and at 1 month after delivery., Results:  The frequency of VTE was 7.5 per 10,000 pregnancies (77 of 103,070) during the pregnancy and post-partum period. After the adjustment of multiple covariates for each factor, endometriosis and recurrent pregnancy loss (RPL) were identified as novel independent risk factors for VTE. Adjusted odds ratios were as follows: 2.70 (95% confidence interval, 1.21-6.00) for endometriosis and 6.13 (2.48-15.16) for RPL. Threatened abortion, threatened pre-term birth, pre-term birth and caesarean section were ascertained to be risk factors for VTE., Conclusion:  Careful attention should be given to novel predictors, such as endometriosis and a history of RPL, to prevent VTE during the pregnancy and post-partum period., Competing Interests: M.S.-O. received grants from the Japanese Ministry of Education, Science, and Technology for conducting studies on the topic of RPL in the different patient population, and payment for lectures from Kaken Pharmaceutical Co. Ltd., Kissei Pharmaceutical Co., Aska Pharmaceutical Co. Ltd., Sekisui Medical Co. Ltd. and Siemens Japan. The remaining authors report no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Despite the increasing incidence of acute coronary syndrome (ACS) in Japan, its prognosis has improved. However, there is a paucity of longitudinal registry data providing trends of in-hospital care and prognosis of ACS in Japan. ACS patients undergoing percutaneous coronary intervention (PCI) included in the Shinken Database 2004-2014 were divided into two groups according to admission year (2004-2009, n = 390; 2010-2014, n = 328). Patient characteristics, lesion/procedure characteristics, medications at discharge, all-cause mortality, cardiovascular death, acute myocardial infarction (AMI), target lesion revascularization (TLR), re-PCI to new lesion, and coronary artery bypass graft (CABG) within 2 years after discharge were compared between the groups. Prevalence of hypertension, dyslipidemia, and dual antiplatelet/statin prescription increased significantly between periods. Usage of second-generation drug-eluting stents (DES) increased markedly between the two periods (2.6, 66.8%), while those of bare metal stents (64.4, 26.5%) and first-generation DES (25.6, 1.5%) decreased (all, p < 0.01). Two-year event-free survival rate increased for all-cause mortality (94.6-98.3%, p = 0.01), TLR (79.4-96.1%, p < 0.01), and re-PCI to new lesion (87.3-95.1%, p < 0.01). There were no significant differences in cardiovascular death, AMI, or CABG between the two periods. The event-free rates for TLR and re-PCI to new lesion in ACS patients have increased over the last decade in Japan. These observations should be confirmed in larger, longitudinal, multicenter registries.

Problem: Several studies have reported the increased risk of preterm birth, premature rupture of membranes, and low birth weight in patients with recurrent pregnancy loss (RPL). There have been a limited number of large population-based studies examining adverse pregnancy and perinatal outcome after RPL. Multiple-imputed analyses (MIA) adjusting for biases due to missing data is also lacking., Method of Study: A nationwide birth cohort study known as the "Japan Environment and Children's Study (JECS)" was conducted by the Ministry of the Environment. The subjects consisted of 104 102 registered children (including fetuses or embryos)., Results: No increased risk of a congenital anomaly, aneuploidy, neonatal asphyxia, or a small for date infant was observed among the children from women with a history of RPL. A novel increased risk of placental adhesion and uterine infection was found. The adjusted ORs using MIA in women with three or more PL were 1.76 (95% CI, 1.04-2.96) for a stillbirth, 1.68 (1.12-2.52) for a pregnancy loss, 2.53 (1.17-5.47) for placental adhesion, 1.87 (1.37-2.55) and 1.60 (.99-2.57) for mild and severe hypertensive disorders of pregnancy, respectively, 1.94 (1.06-3.55) for uterine infection, 1.28 (1.11-1.47) for caesarean section and .86 (.76-.98) for a male infant., Conclusion: MIA better quantified the risk, which could encourage women who might hesitate to attempt a subsequent pregnancy., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The predictive role of E/e' on ischemic stroke (IS) and atrial fibrillation (AF) in Japanese patients without AF are unclear., Methods and Results: Shinken database includes all the new patients visiting the Cardiovascular Institute Hospital in Tokyo, Japan. E/e' has been routinely measured since 2007. Patients without AF for whom E/e' was measured at the initial visit between 2007 and 2014 (n=11 477, mean age 57.2 years old, men 59.5%) were divided into E/e' tertiles (<8.04, 8.04-11.00, >11.00). During the mean follow-up period of 1.8 years, 58 IS and 140 new appearances of AF were observed. High E/e' tertile was associated with more prevalence of atherothrombotic risks. The cumulative incidence of IS events and new appearance of AF at 6 years in low, middle, and high E/e' tertiles were 0.5%, 1.4%, and 3.0%/year (log-rank test, p<0.001), and 2.5%, 2.9%, and 4.2%/year (log-rank test, p=0.007), respectively. In multivariate analysis, high E/e' tertile was independently associated with IS (HR, 2.857, 95%CI 1.257-6.495, p=0.012). Although high E/e' tertile was independently associated with new appearance of AF when adjusted for coexistence of atherothrombotic risk factors (HR, 1.694, 95%CI, 1.097-2.616, p=0.017), the association was attenuated after adjustment for left atrial dimension., Conclusions: E/e' was significantly associated with incidence of IS and new appearance of AF in non-AF patients., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Variability in the international normalized ratio (INR) of prothrombin time has been suggested to be related to outcome in patients with atrial fibrillation (AF) under warfarin therapy, but its determinants remain unclear.Methods and Results:The study population consisted of 626 AF patients under warfarin therapy in the Shinken Database (n=22,230). INR variability was calculated by Fihn's method. Determinants of high log INR variability (defined as over mean+standard deviation) were determined by logistic regression analyses. Symptomatic heart failure (odds ratio [OR] 3.974, 95% confidence interval [CI] 2.510-6.292), older age (≥75 years old; OR 2.984, 95% CI 1.844-4.826) and severe renal dysfunction (eGFR <30 mL/min/1.73 m 2 ; OR 3.918, 95% CI 1.742-8.813) were identified as independent predictors of high INR variability on multivariate logistic regression analysis., Conclusions: The determinants of INR variability in AF patients under warfarin therapy could assist Japanese clinicians in identifying patients likely to show unstable warfarin control irrespective of the definition of the target INR range.

Background: We previously reported a cross-sectional analysis regarding the relationship between smoking and atrial fibrillation (AF) in a single hospital-based cohort with Japanese patients, but the effect of cessation of smoking and/or total tobacco consumption were unclear., Methods and Results: We used data from the Shinken Database 2004-2011 (men/women, n=10,714/6803, respectively), which included all new patients attending the Cardiovascular Institute between June 2004 and March 2012. After excluding those previously diagnosed with AF (n=2296), 15,221 patients (men/women, n=9016/6205) were analyzed. During the follow-up period of 2.0±2.1 years (range 0.0-8.1), the incidence rates of new AF in smokers and non-smokers were 9.0 and 5.0 per 1000 patient-years, respectively. In adjusted models with Cox regression analysis, smokers were independently associated with new AF [hazard ratio (HR) 1.47, 95% confidence interval (CI) 1.09-2.00]. Also, current smokers (HR 1.81, 95% CI 1.17-2.79) and smokers with Brinkman index ≥800 (HR 1.69, 95% CI 1.05-2.70) were independently associated with new AF. However, in current smokers, the HRs were not different by Brinkman index (Brinkman index <800/≥800; HR 1.81/1.82, 95% CI 1.07-3.05/0.94-3.51, respectively)., Conclusions: Smoking was independently associated with the first-appearance of AF in patients in sinus rhythm, especially when the patients continued their smoking habit. However, in patients who continued smoking, difference by total tobacco consumption was not observed, suggesting the significance of cessation of smoking for preventing AF. Our data are limited because of a single hospital-based nature and a relatively short observation period., (Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Repeated hospitalization due to acute decompensated heart failure (HF) is a pandemic health problem in Japan. However, it is difficult to predict rehospitalization after discharge for acute decompensated HF. We used a single hospital-based cohort from the Shinken Database 2004-2012, comprising all new patients (n = 19,994) who visited the Cardiovascular Institute Hospital. A total of 282 patients discharged after their first acute HF admission were included in the analysis. The median follow-up period was 908 ± 865 days. Of these patients, rehospitalization due to worsening HF occurred in 55 patients. The cumulative rate of rehospitalization was 17.5% at 1 year, 21.4% at 2 years, and 25.5% at 3 years. Patients with rehospitalization were older than those without rehospitalization. Prevalence of diabetes mellitus (DM) was more common in patients with rehospitalization. Average heart rate (HR) tended to be higher in patients with rehospitalization. Loop diuretics were more commonly used at hospital discharge in patients with rehospitalization. Multivariate Cox regression analysis revealed that age ≥ 75 years, DM, HR ≥ 75 bpm at discharge, and use of loop diuretics at discharge were independent predictors for rehospitalization. The number of these independent risk factors could be used to clearly discriminate between the HF rehospitalization low-, middle- and high-risk patients. HF rehospitalization commonly occurred in patients who were discharged after their first acute HF admission. Older age, DM, increased HR, and loop diuretics use at discharge were independently associated with HF rehospitalization. By simply counting these risk factors, we might be able to predict the risk of HF rehospitalization after discharge.

Functional mitral regurgitation (MR) is frequently associated with left ventricular systolic dysfunction (LVSD). Ventricular volume overload that occurs in patients with MR may lead to a progression of myocardial dysfunction. However, the prevalence and clinical outcomes of functional MR in Japanese patients with LVSD remain unclear. The aim of the present study is to clarify the prevalence and prognosis of functional MR in Japanese LVSD patients in the contemporary era. We followed patients with LVSD (LV ejection fraction (LVEF) ⩽ 40%) who were listed within a single, hospital-based cohort in the Shinken Database from 2004 to 2011, which was composed of all new patients (n = 17,517) who visited the Cardiovascular Institute. A total of 506 patients were included: 86 FMR (moderate-to-severe functional MR) patients and 420 non-FMR (none or mild functional MR) patients. FMR patients were older, had lower rates of hypertension and ischemic heart disease but had higher rates of chronic kidney disease, dilated cardiomyopathy and New York Heart Association III/IV classification. FMR patients had higher brain natriuretic peptide levels and lower LVEF. The Kaplan-Meier curves revealed that the incidence of all-cause death, cardiovascular death and heart failure (HF) admission was significantly higher in FMR patients. The presence of FMR was independently associated with a significantly higher risk of composite end point, including all-cause death and/or HF admission (hazard ratio 1.551, 95% confidence interval 1.045-2.303, P = 0.029). FMR was common in Japanese patients with LVSD and was associated with adverse long-term outcomes. Future study is warranted to establish the optimal therapeutic strategy for FMR and LVSD.

Background and Aim of the Study: Recent brain complications (e.g., bleeding or infarction) in patients with active infective endocarditis (AIE) are recognized as a contraindication for early surgery. Nafamostat mesilate (NM) is a synthetic protease-inhibiting agent that has not only potent inhibitory activity against coagulation factors (Xlla, Xa) but also an anti-inflammatory action. Herein is reported the authors' successful surgical experience using NM with low-dose heparinization in patients with AIE complicated by recent cerebral complications., Methods: Twenty-eight patients (mean age 54.9 +/- 18.7 years) who had undergone surgery for AIE of the native valve (n = 21) or prosthetic valve (n = 7) were reviewed retrospectively. AIE was present in the aortic (n = 8), mitral (n = 16), aortic/mitral (n = 4) and tricuspid (n = 1) valves. Twenty-two of 28 patients had preoperative stroke, and six had active brain bleeding. Surgery was performed at a mean of 2.4 +/- 2.1 days after the onset of stroke. NM (209 +/- 152 mg) with low-dose heparin (3796 +/- 1218 IU; 67.4 +/- 20.3 IU/kg) was used for anticoagulation during cardiopulmonary bypass (CPB). The activated clotting time (ACT) was maintained at 350-450 s by the precise administration of NM into a cardiotomy reservoir (0.5 mg/kg/h) and a venous reservoir (sliding controlled dose at 1.5 mg/kg/h)., Results: The CPB time was 181.3 +/- 92.6 min. Five patients (17.8%) died during hospitalization due to persistent sepsis (n = 3), brain death caused by massive brain embolism before CPB establishment (n = 1), and pneumonia (n = 1). There was no further aggravation of intracranial bleeding, and no new hemorrhagic stroke., Conclusion: Nafamostat mesilate, administered in conjunction with low-dose heparinization, served as an effective anticoagulant for early surgery in patients with AIE complicated by stroke, and caused no further deterioration of the cerebral lesions.

Functional mitral regurgitation (FMR) is a common and critical condition in patients with heart failure (HF); however, the prevalence and clinical outcome of FMR in Japanese real-world clinical practice remain unclear. Within a single hospital-based cohort in the Shinken Database 2004-2011, which comprised all new patients (n = 17,517) who visited the Cardiovascular Institute, we followed symptomatic HF patients. A total of 1,701 patients were included: 104 FMR patients (who had moderate to severe FMR) and 1,597 non-FMR patients (who had none or mild FMR). FMR patients had lower rates of hypertension and dyslipidemia, but higher rates of dilated cardiomyopathy, atrial fibrillation, and New York Heart Association functional class III/IV. FMR patients had higher levels of brain natriuretic peptide and lower left ventricular function. Use of cardiovascular drugs was more common among FMR patients. Kaplan-Meier curves revealed that the incidences of all-cause death, cardiovascular death, and admission for HF were significantly higher in FMR patients. The adjusted Cox regression analysis showed that significant FMR was associated with higher incidences of all-cause death [hazard ratio (HR) 2.179, 95 % confidence interval (CI) 1.266-3.751; P = 0.005], cardiovascular death (HR 2.371, 95 % CI 1.157-4.858; P = 0.018), and admission for HF (HR 1.819, 95 % CI 1.133-2.920; P = 0.013). FMR was common in Japanese symptomatic HF patients and was associated with adverse long-term outcomes. Establishing optimal therapeutic strategies for FMR is warranted.

Background: Limb malformations are rare disorders with high genetic heterogeneity. Although multiple genes/loci have been identified in limb malformations, underlying genetic factors still remain to be determined in most patients., Methods: This study consisted of 51 Japanese families with split-hand/foot malformation (SHFM), SHFM with long bone deficiency (SHFLD) usually affecting the tibia, or Gollop-Wolfgang complex (GWC) characterized by SHFM and femoral bifurcation. Genetic studies included genomewide array comparative genomic hybridization and exome sequencing, together with standard molecular analyses., Results: We identified duplications/triplications of a 210,050 bp segment containing BHLHA9 in 29 SHFM patients, 11 SHFLD patients, two GWC patients, and 22 clinically normal relatives from 27 of the 51 families examined, as well as in 2 of 1,000 Japanese controls. Families with SHFLD- and/or GWC-positive patients were more frequent in triplications than in duplications. The fusion point was identical in all the duplications/triplications and was associated with a 4 bp microhomology. There was no sequence homology around the two breakpoints, whereas rearrangement-associated motifs were abundant around one breakpoint. The rs3951819-D17S1174 haplotype patterns were variable on the duplicated/triplicated segments. No discernible genetic alteration specific to patients was detected within or around BHLHA9, in the known causative SHFM genes, or in the exome., Conclusions: These results indicate that BHLHA9 overdosage constitutes the most frequent susceptibility factor, with a dosage effect, for a range of limb malformations at least in Japan. Notably, this is the first study revealing the underlying genetic factor for the development of GWC, and demonstrating the presence of triplications involving BHLHA9. It is inferred that a Japanese founder duplication was generated through a replication-based mechanism and underwent subsequent triplication and haplotype modification through recombination-based mechanisms, and that the duplications/triplications with various haplotypes were widely spread in Japan primarily via clinically normal carriers and identified via manifesting patients. Furthermore, genotype-phenotype analyses of patients reported in this study and the previous studies imply that clinical variability is ascribed to multiple factors including the size of duplications/triplications as a critical factor.

The International Consortium for Evidence-Based Perfusion (ICEBP) is a collaborative group whose mission is to improve, continuously, the delivery of care and outcomes for patients undergoing cardiac surgery. To achieve this end, the ICEBP supports the development of perfusion registries to evaluate clinical practices and has established evidence-based guidelines for perfusion. The Japanese Society of Extra-Corporeal Technology in Medicine (JaSECT) developed a perfusion registry to examine variation in perfusion practice in Japan. A pilot study was designed to determine the rate and accuracy of data extraction from patients' medical records and perfusion practice records and the subsequent entry of data into the registry form. We designed an input matching test using medical records and perfusion records from a sample of patients. Five institutions participated in data. extraction and entry from 10 randomly selected case records. Perfusionists entered data in the registry form in accordance with the instruction manual prepared by the JaSECT guideline committee. The time taken to input every case in the registry was measured. An interview-based survey was carried out across institutions after the completion of the pilot. The time required for data entry stabilized after approximately five cases to a rate that was 40% of the first case entry time. Data entered into the registry by perfusionists for multiple-choice items were accurate 65% of the time and accurate 25% of the time for numerical data. The interview-based survey identified a total of 38 opportunities for improvement in the input form and 58 recommended changes for the instruction manual. The accuracy of data may be improved by developing a method allowing the objective detection of deficient data when present in the perfusion case record by developing automatic data acquisition from the automatic perfusion recording system currently in use, and by changing as many numerical value input items as possible to multiple-choice items.

Revascularization of an initially non-target site due to its progression as a new culprit lesion has emerged as a new therapeutic target of coronary artery disease (CAD) in the era of drug-eluting stents. Using the Shinken database, a single-hospital-based cohort, we aimed to clarify the incidence and prognostic factors for progression of previously non-significant coronary portions after prior percutaneous coronary intervention (PCI) in Japanese CAD patients. We selected from the Shinken database a single-hospital-based cohort of Japanese patients (n = 15227) who visited the Cardiovascular Institute between 2004 and 2010 to undergo PCI. This study included 1,214 patients (median follow-up period, 1,032 ± 704 days). Additional clinically driven PCI to treat previously non-significant lesions was performed in 152 patients. The cumulative rate of new-lesion PCI was 9.5 % at 1 year, 14.4 % at 3 years, and 17.6 % at 5 years. There was no difference in background clinical characteristics between patients with and without additional PCI. Prevalence of multi-vessel disease (MVD) (82 vs. 57 %, p < 0.001) and obesity (47 vs. 38 %, p = 0.028) were significantly higher and high-density lipoprotein cholesterol (HDL) level (51 ± 15 vs. 47 ± 12 mg/dl, p < 0.001) was significantly lower in patients with additional PCI than those without. Patients using insulin (6 vs. 3 %, p = 0.035) were more common in patients with additional PCI. Multivariate analysis showed that MVD, lower HDL, and insulin use were independent determinants of progression of new culprit coronary lesions. In conclusion, progression of new coronary lesions was common and new-lesion PCI continued to occur beyond 1 year after PCI without attenuation of their annual incidences up to 5 years. Greater coronary artery disease burden, low HDL, and insulin-dependent DM were independent predictors of progression of new culprit coronary lesions.

Japan has become an aging society, resulting in an increased prevalence of coronary artery disease. However, clinical outcomes of elderly Japanese patients after percutaneous coronary intervention (PCI) remain unclear. Of the 15,227 patients in the Shinken Database, a single-hospital-based cohort of new patients, 1,214 patients who underwent PCI, was evaluated to determine the differences in clinical outcomes between the elderly (≥75 years) (n = 260) and the non-elderly (<75 years) (n = 954) patients. A major adverse cardiac event (MACE) was defined as a composite end point, including all-cause death, myocardial infarction (MI), and target lesion revascularization. Male gender and obesity were less common, and the estimated glomerular filtration rate (eGFR) was significantly lower in the elderly than in the non-elderly. Left ventricular ejection fraction (LVEF) was comparable between these groups. Left main trunk disease and multivessel disease were more common in the elderly than in the non-elderly group. Occurrence of MACE was frequent, and the incidences of all-cause death, cardiac death, and the admission rate for heart failure were significantly higher in the elderly patients. Multivariate analysis showed that prior MI, low eGFR, and poor LVEF were independent predictors for all-cause death in the elderly patients. Elderly patients had worse clinical outcomes than the non-elderly patients. Low eGFR and LVEF were independent predictors of all-cause death after PCI, suggesting that left ventricular dysfunction and renal dysfunction might synergistically contribute to the adverse clinical outcomes of the elderly patients undergoing PCI.

Background:  Prothrombin time (PT) distribution in Japanese nonvalvular atrial fibrillation (NVAF) patients under rivaroxaban therapy remains to be clarified., Methods and Results:  Between May 2012 and July 2013, 115 NVAF patients received rivaroxaban (PT was measured in 94; reagent: recombiplastin). In these patients, (1) PT values were distributed widely from patient to patient and from peak to trough, (2) the time-dependence was obscure with sampling at any time in the outpatient clinic, and (3) the incidence of adverse events was too low for analyzing the relation with PT., Conclusions:  We report the distribution of PT for Japanese NVAF patients under rivaroxaban therapy in real-world clinical practice.

Statins reduce cardiovascular morbidity and mortality from coronary artery disease (CAD). However, the effects of statin therapy in patients with CAD and chronic kidney disease (CKD) remain unclear. Within a single hospital-based cohort in the Shinken Database 2004-2010 comprising all patients (n = 15,227) who visited the Cardiovascular Institute, we followed patients with CKD and CAD after percutaneous coronary intervention (PCI). A major adverse cardiovascular and cerebrovascular event (MACCE) was defined by composite end points, including death, myocardial infarction, cerebral infarction, cerebral hemorrhage, and target lesion revascularization. A total of 391 patients were included in this study (median follow-up time 905 ± 679 days). Of these, 209 patients used statins. Patients with statin therapy were younger than those without. Obesity and dyslipidemia were more common, and the glomerular filtration rate (GFR) was significantly higher, in patients undergoing statin treatment. MACCE and cardiac death tended to be less common, and all-cause death was significantly less common, in patients taking statins. Multivariate analysis showed that low estimated GFR, poor left ventricular ejection fraction, and the absence of statin therapy were independent predictors for all-cause death of CKD patients after PCI. Statin therapy was associated with reduced all-cause mortality in patients with CKD and CAD after PCI.

Background: This study investigated the progression of paroxysmal atrial fibrillation (AF) to the persistent form in Japanese asymptomatic AF patients., Methods and Results: Data were derived from a single hospital-based cohort in the Shinken Database 2004-2012 (n=19,994), in which 1,176 patients were diagnosed as having paroxysmal AF. AF progression occurred in 115 patients (6.0%/year) during the mean follow-up period (1,213±905 days). Although patients who were asymptomatic at the initial visit (n=468) had a low-risk profile compared with symptomatic patients, they had greater AF progression at follow-up (unadjusted hazard ratio, 1.611; 95% CI: 1.087-2.389; P=0.018). Absence of symptoms, male sex, and cardiomyopathy were independent predictors for AF progression in the multivariate model. It was noted that asymptomatic patients were less likely to undergo pulmonary vein isolation (PVI). In addition, the interaction term between asymptomatic AF and absence of PVI could be another independent predictor for AF progression. Prognosis was similar between asymptomatic and symptomatic patients with AF., Conclusions: Irrespective of low-risk profile, patients with asymptomatic paroxysmal AF had greater progression of AF compared with symptomatic patients. This paradoxical result appeared to be the result of less intensive clinical management, including invasive rhythm control.

Frequent supraventricular extrasystoles (SVEs) are associated with the subsequent first-time appearance of atrial fibrillation (AF) and ischemic stroke. The aim of this study was to investigate the combined role of SVEs and an AF-related risk score for ischemic stroke, the CHADS2 score, on the occurrence of new AF in patients in sinus rhythm. The Shinken Database 2004-2010 lists 3,263 patients who underwent 24-hour Holter monitoring. A total of 2,589 patients were analyzed, after excluding 674 patients previously diagnosed with AF. Frequent SVEs were defined as ≥102 beats/day (the top quartile) and the presence of a clinical background for a CHADS2 score ≥2 points as a high CHADS2 score. During the mean follow-up period of 571.4 ± 606.4 days, new AF occurred in 38 patients (9.4 per 1,000 patient-years). The incidence of new AF was 2.7 and 37.7 per 1,000 patient-years for patients with nonfrequent SVEs (<102 beats/day) and low CHADS2 scores and those with frequent SVEs and high CHADS2 scores, respectively. Multivariate Cox regression analysis showed that the hazard ratio for frequent SVEs and a high CHADS2 score compared with nonfrequent SVEs and a low CHADS2 score was 9.49 (95% confidence interval 3.20 to 28.15, p <0.001), even after adjustment for gender, age, medications, and echocardiographic parameters. In conclusion, frequent SVEs and a high CHADS2 score independently and synergistically predict the first-time appearance of AF in patients in sinus rhythm, indicating an approximately 10-fold higher risk. Patients meeting these criteria should have more aggressive early intervention for preventing AF., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Tobacco smoking is a well-known risk factor for cardiovascular disease, but controversial results have been reported regarding its relationship with atrial fibrillation (AF). Moreover, no study on the relationship between smoking and AF has yet been undertaken in a Japanese context., Methods and Results: We used data from the Shinken Database 2004-2011 (men/women, n=10,714/6,803, respectively), which included all new patients attending the Cardiovascular Institute between June 2004 and March 2012. AF was diagnosed in 1,698 and 598 men and women, respectively. In men, smokers were more prevalent in the AF than in the non-AF group (54.5% vs. 44.7%), whereas in women the prevalence of smokers was similar between AF and non-AF groups (14.4% vs. 15.4%). This discrepancy between the sexes seems to derive from a characteristic distribution pattern of smoking habit in women. After adjustment for various cofactors, smoking was independently associated with AF (odds ratio 1.54; 95% confidence interval 1.35-1.75; P<0.001) without a significant interaction between sex categories (P=0.195)., Conclusions: Smoking was independently associated with AF without a significant interaction between sex categories among Japanese patients visiting a cardiovascular hospital. Further studies using a prospective cohort design are required to confirm a causal link between smoking and AF in Japanese patients.

Background/aims: Colon interposition is the most commonly used method of esophageal reconstruction when the stomach cannot be used; however, this method may cause surgical complications such as anastomotic leakage and sepsis due to colon necrosis. Therefore, many surgeons use a retrosternal or subcutaneous route because it is easier to manage the subcutaneous drainage when anastomotic leakage occurs. However, some researchers have reported that the posterior mediastinal route provides better long-term functional outcomes after surgery than the anterior mediastinal route. Thus, in this study, we compared these reconstruction routes used for colon interposition, with or without the supercharge technique, in patients with a history of distal gastrectomy, who have undergone colon interposition after esophagectomy., Methodology: We retrospectively studied 30 patients who underwent esophagectomy with colon interposition. These patients were divided into 2 groups based on the reconstruction route: the anterior mediastinal or subcutaneous route (A group), or the posterior mediastinal route (R group)., Results: Anastomotic leakages were observed in 4 patients (26.7%) in the A group and in 1 patient (6.7%) in the R group., Conclusions: Ischemia is not always the result of arterial failure, but may also originate from venous blood flow impairment due to injury or distortion of veins.

Background/aims: Marginal ulceration and delayed gastric emptying are considerable problems after pancreaticoduodenectomy. Helicobacter pylori (HP) are well known to be associated with gastritis, gastric ulcer and gastric cancer. Thus, we studied the relationship between marginal ulceration and delayed gastric emptying in the early postoperative period after pancreaticoduodenectomy with pancreaticogastrostomy., Methodology: We retrospectively studied 58 patients who underwent pancreaticoduodenectomy with pancreaticogastrostomy. On the basis of the grade of delayed gastric emptying, these patients were divided into 2 groups-WS group; without/with slight delayed gastric emptying and MS group; moderate/severe delayed gastric emptying., Results: Two patients (3.4%) developed postoperative marginal ulcer, these 2 patients had no HP infection; moreover, they belonged to the MS group. Five patients in the WS group were infected with HP; although, postoperative marginal ulceration did not develop in these 5 patients., Conclusions: Delayed gastric emptying might be a stronger promoting factor of postoperative marginal ulcer after pancreaticoduodenectomy with pancreaticogastrostomy rather than HP infection and prevention of delayed gastric emptying is important to reduce the occurrence rate of postoperative marginal ulcer. Our modified subtotal stomach-preserving pancreaticoduodenectomy is a useful procedure for preventing delayed gastric emptying and postoperative marginal ulcer after pancreaticoduodenectomy with pancreaticogastrostomy.

Background/aims: A high incidence of hyperbilirubinemia and an increased incidence of gallbladder disorders after esophagectomy have been reported. Moreover, several studies have documented an increased incidence of gallbladder disease in patients receiving long-term total parenteral nutrition. We studied the incidence of cholecystitis and cholestasis and hyperbilirubinemia associated with total parenteral nutrition after esophagectomy., Methodology: We retrospectively studied 42 patients who underwent esophagectomy. These patients were divided into 2 groups: the hyperbilirubinemia group and the non-hyperbilirubinemia group. The incidence of cholecystitis or cholestasis after the surgery was compared between the 2 groups., Results: The mean total serum bilirubin level of the hyperbilirubinemia group (2.40±0.35mg/dL) was significantly higher than that of the non-hyperbilirubinemia group (1.20±0.34mg/dL; p<0.0001). No significant differences were observed between the 2 groups with respect to the mean duration for which total parenteral nutrition was required around the time of the operation (i.e. pre- and postoperatively) and the incidence rate of cholecystitis or cholestasis after esophagectomy., Conclusions: Hyperbilirubinemia after esophagectomy was frequently observed; however, it may not contribute to gallbladder problems. We suggest that parenteral modalities such as tube feeding should be initiated soon after surgery to prevent gallbladder problems after esophagectomy.

Background/aims: The management of peptic ulcers has dramatically changed and the incidence of elective surgery for gastroduodenal peptic ulcers has markedly decreased; hence, the incidence of emergency surgery for perforated peptic ulcers has slightly increased. In select cases, conservative therapy can be used as an alternative for treating perforated gastroduodenal ulcers. In this study, we evaluated the efficacy of percutaneous abdominal drainage for the conservative treatment of perforated gastroduodenal ulcers., Methodology: We retrospectively studied 51 patients who had undergone conservative therapy for perforated gastroduodenal ulcers. These patients were divided into 2 groups on the basis of the initial treatment with conservative therapy with or without percutaneous drainage: group PD included patients who had undergone percutaneous drainage and group NPD, patients who had undergone non-percutaneous drainage., Results: In the PD group, 14.3% (n=3) of the patients did not respond to conservative therapy, while this value was 43.3% (n=13) in the NPD group. The 2 groups differed significantly with respect to conversion from conservative therapy to surgery (p<0.0352)., Conclusions: Conservative therapy for perforated gastroduodenal ulcers should be performed only in the case of patients meeting the required criteria; its combination with percutaneous intraperitoneal drainage is effective as initial conservative therapy.

Background/aims: Staging laparoscopy is useful for increasing the accuracy of preoperative tumor staging. Diagnostic laparoscopy has therefore been introduced to prevent unnecessary laparotomy in patients with unresectable cancers. However, the technique of laparoscopic observation remains controversial. In this study, we determined the efficacy of hand-assisted laparoscopic staging., Methodology: We retrospectively studied 44 patients who underwent conventional (LS group) or hand-assisted laparoscopic staging (HALS group)., Results: The T factors of the TNM staging system was accurately determined in 95% of the patients in the HALS group and 58.3% of the patients in the LS group (p<0.0060). A total of 33.3% tumors in the LS group and 10% in the HALS group were judged to be unresectable. The overall mean survival was longer in the HALS group (20.3±12.2 months) than in the LS group (15.8±11.9 months)., Conclusions: Laparoscopic diagnosis and staging of advanced gastric cancer are reliable. Moreover hand-assisted laparoscopic staging enables the accurate assessment of tumor resectability.

Background/aims: Cholecystectomy as a factor causing common bile duct (CBD) dilatation has been debated. The aim of this study was to investigate CBD dilatation after cholecystectomy in patients with a preoperative CBD diameter of <6mm., Methodology: We retrospectively analyzed the cases of 101 patients who underwent cholecystectomy. These patients were divided into 2 groups, the open cholecystectomy group (OC group) and the laparoscopic cholecystectomy group (LC group)., Results: The postoperative mean CBD diameter was 5.80±0.49mm in the OC group and 5.75±0.47mm in the LC group; the diameters were not significantly different between the 2 groups (p<0.6699). With regard to the change in body weight after surgery, in the OC group 71.1%, patients gained weight, 20% showed no change and 8.9% lost weight; the corresponding numbers in the LC group were 75%, 23.2% and 1.8% patients, respectively. Thus, there were no significant differences in terms of weight changes between the 2 groups (p<0.6607, p<0.6973 and p<0.1690, respectively)., Conclusions: For patients with preoperative CBD diameters of <6mm no compensatory dilatation occurs after open or laparoscopic cholecystectomy.

Infestation of young apple fruits by the larvae of the peach fruit moth, Carposina sasakii Matsumura (Lepidoptera: Carposinidae), was studied by a small dedicated micro-magnetic resonance imaging (MRI) apparatus using the three-dimensional (3D) gradient-echo method and the two-dimensional (2D) and 3D spin-echo methods. Changes from a young larva at 1.8 mm in length to a mature one ready to leave the fruit were observed in relation to the progression of infestation of the fruit tissues. The trace of larva intrusion was demonstrated by a series of sliced images in the 3D image data of an infested fruit, where it entered from outside the calyx, and migrated to near the vasculature around the carpel through the core. The small, dedicated MRI device was proven useful for ecological studies of the growth and movement of insect larvae in their food fruits. It can also be applied to detect the infestation of small fruits by insect larvae.

Background: While many cases of latex allergy have been reported in Japanese health care workers (HCWs) since 1992, there have been no follow-up studies after removing latex from the workplace. We had previously replaced all working environment latex gloves and latex products with low-allergen or non-latex products. The purpose of the investigation was to evaluate the benefits of the latex allergy countermeasures that were taken in our hospital, and the effects of life guidance education., Methods: We investigated 16 latex-allergic HCWs in our hospital. We gave them a detailed questionnaire and tested them by a skin prick test (SPT) with latex extract and specific IgE antibodies against latex using the Pharmacia CAP RAST system, RAST FEIA. We compared these results with earlier results from the time of diagnosis., Results: According to the questionnaire, none of the HCWs had changed their work habits, though all were avoiding the use of latex products as much as possible. Of the 16 patients, 81.2% were eating foods for which cross reactivity with latex has been reported. However, the foods had not induced severe allergic symptoms. In the SPT, 62.5% of scores decreased and 81.2% of patients had decreases in specific IgE antibody levels., Conclusions: After avoiding latex products and following our educational suggestions, the patients' allergy symptoms had generally improved. This indicates that our countermeasures against latex allergy were largely successful.

Carcinogenicity and chronic toxicity of 1,4-dichloro-2-nitrobenzene (DCNB) were examined by feeding each group of 50 F344 rats and 50 BDF1 mice of both sexes a DCNB-containing diet at a concentration of 0 (control), 320, 800 or 2,000 ppm (w/w) for 2 yr. In rats, incidences of hepatocellular adenomas and carcinomas and their combined incidence were increased in the 2,000 ppm-fed males, together with increased incidence of basophilic cell foci in the 800 and 2,000 ppm-fed males. A dose-related increase in combined incidences of renal cell adenomas and carcinomas was noted. Incidence of Zymbal gland adenomas tended to increase in the 2,000 ppm-fed males. In mice, incidences of hepatocellular adenomas in the 800 and 2,000 ppm-fed females and hepatocellular carcinomas in the 2,000 ppm-fed males and in the 800 and 2,000 ppm-fed females were increased. Incidence of hepatoblastomas was increased in all DCNB-fed males and in the 2,000 ppm-fed females. Signs of chronic toxicity were characterized by centrilobular hypertrophy of hepatocytes with nuclear atypia in mice, increased relative liver weight in rats, a dose-related increase in incidences of chronic progressive nephropathy with advanced grades of severity in male rats, and decreased hemoglobin concentration and hematocrit accompanied by increased bone marrow hematopoiesis in female rats. Carcinogenic activity of DCNB was evaluated for the three different tumors, and sensitive signs of the chronic toxicity were dis-

For the first time in Japan, a large-scale survey to investigate awareness of latex allergy was carried out, targeting all health care workers at Fujita Health University School of Medicine (total 1512 people). At first, we used questionnaires to collect information regarding the level of awareness of latex allergy as well as the incidence of clinical symptoms when using natural rubber products. The results of the survey revealed that approximately 85% of respondents were aware of latex allergy. Among all respondents, approximately 19% had actual experience with clinical symptoms. As a result of skin tests conducted on respondents who had acknowledged clinical symptoms, 44 people (total 3.3%) were diagnosed with latex allergy. In addition, the results revealed that people who were diagnosed with latex allergy tended to suffer atopic dermatitis and hand eczema. Furthermore, it became evident that health care workers whose work environment involved frequent exposure to natural rubber products showed a higher incidence of latex allergy. We demonstrated that a specific IgE assay was not sufficiently sensitive for diagnosing latex allergy. However, skin tests such as prick and use tests were confirmed to be effective diagnostic measures for latex allergy.

CD19 regulates the signaling for B lymphocyte development, activation and proliferation. In mice, CD19 deficiency and overexpression were shown to result in hypogammaglobulinemia and autoantibody production, respectively. In the present study, we screened for the polymorphisms of CD19, and examined the detected polymorphisms for the association with rheumatoid arthritis (RA), Crohn's disease and systemic lupus erythematosus (SLE). Two SNPs, c.705G>T (P235P and IVS14-30C>T, were decreased (P = 0.0096 and P = 0.028, respectively), in SLE. A GT repeat polymorphism, c.*132(GT)(12-18), was detected within the 3'-untranslated region, and individuals with > or =15 times repeat was significantly increased in the independent two groups of Japanese SLE patients (P = 0.011 and P = 0.035, respectively); the overall difference between total SLE and controls was striking (P = 0.0061). No association was observed for RA and Crohn's disease. In addition, no variations other than the common polymorphisms were detected in four patients with common variable immunodeficiency, the phenotype of which resembles CD19 deficient mice. In Caucasian SLE families, this GT repeat polymorphism was rare. CD19 mRNA level in the isolated peripheral blood B lymphocytes was lower in individuals possessing (GT)(15-18) alleles compared with those without these alleles, both in controls and in SLE patients; however, the difference did not reach statistical significance. These results suggested that either the slight reduction in the CD19 mRNA level associated with the elongation of GT repeat, or an allele of another locus in linkage disequilibrium with CD19 (GT)(15-18), may be associated with susceptibility to SLE in Japanese.