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Management of bleeding during endoscopic submucosal dissection (ESD) is critical. Red Dichromatic Imaging (RDI), a novel image-enhanced endoscopy technology, has been reported to improve the visibility of deep vessels and bleeding source compared to white light imaging (WLI). We hypothesized that using RDI during the entire cutting process (full time RDI ESD: FTR-ESD), higher R0 resection rate, shorter procedure time and fewer complications could be achieved. Therefore, the aims of the present study were to investigate the efficacy and safety of FTR-ESD.This retrospective observational study included a total of 82 consecutive patients who underwent ESD by a single expert endoscopist for 40 esophageal, 17 gastric and 25 colorectal cancers at our institution from January 2018 to March 2021. The clinicopathological data were collected from patients' medical records and the treatment outcomes were analyzed according to the treatment phase (early; 57 WLI-ESD and late; 25 FTR-ESD).The median of the greatest diameter of resected specimen was 40.0 mm. The median procedure time was relatively shorter in the FTR-ESD group (35 min) than in the WLI-ESD group (40 min), but the difference was not statistically significant (p = 0.34). The median dissection speed in the FTR-ESD group (27.23 mmFTR-ESD significantly increases the dissection speed compared to WLI-ESD. FTR-ESD can be performed safely and therapeutic outcomes in FTR-ESD are comparable with WLI-ESD. A further multicenter prospective study is warranted to confirm our results.

Background and aim An injection solution is required to create a submucosal cushion (SMC) for safe endoscopic resection procedures. The aim of this preliminary animal study was to clarify the safety and efficacy of a novel fully synthetic and self-assembled peptide (FSSP) solution as a submucosal injection material (SMIM). Method To compare the submucosal-lifting properties, 0.3% FSSP, Eleview®, sodium hyaluronate acid solution (SHA) and normal saline (NS) were randomly injected using an injection needle into the submucosa of exposed stomach and colon in five living dogs in a blind fashion. The mean height, and volume of SMCs were measured using a digital caliper immediately and 10, 20, 30, and 40 min after injecting each solution. All resected specimens were examined histopathologically. Results In both the colon and stomach, ANOVA for repeated measures showed the significant interaction between time and solution for the time-dependent change in the height. In the colon, FSSP created significantly higher SMC than NS 20 min after injection (p = .0015) and Eleview® and NS 40 min after injection (p = .0009 and p = .0002). Furthermore, FSSP and SHA tended to maintain height and volume when compared to the other two solutions. In the stomach, FSSP and SHA tended to maintain height and volume when compared to the other two solutions. There were no significant differences between the histopathological finding and the injecting solutions used. Conclusion FSSP seems to be useful as a SMIM for endoscopic resection especially in the colon. Further studies are needed prior to clinical use of FSSP.

A new automated diagnostic program for high-resolution esophageal manometry (HREM) has been developed. This diagnostic program could detect locations of landmarks and could make final diagnoses automatically. However, the accuracy of the program is not known. The aim of this study was to evaluate the accuracy of the automated diagnostic program for HREM. A total of 445 studies were enrolled. An HREM system (Starlet®) was used, and esophageal motility was diagnosed using the Chicago classification v3.0. First, the locations of the upper esophageal sphincter, transition zone, lower esophageal sphincter, esophago-gastric junction, crural diaphragm and stomach were determined, and each swallow was checked manually. Then, the parameters of the Chicago classification were calculated using an analytic program of the Starlet, and diagnoses were made by three experts. Second, all study raw data were analyzed again by the automated diagnostic program. Diagnoses made by the program were compared to those made by experts to evaluate the accuracy of the diagnoses. The new diagnostic program could identify the landmarks of each swallow, calculate the parameters and make a final diagnosis within 10 s. The diagnoses made by the automated diagnostic program were not matched to those made by experts in only 10 studies, and the overall accuracy of the new automated diagnostic program thus reached 97.8% (435/445). The new automated diagnostic program for HREM is clinically useful in terms of high diagnostic accuracy and time-saving.

Takumi Kurabayashi,1 Yuki Ideno,2 Kazue Nagai,3 Naho Maruoka,3 Kiyoshi Takamatsu,4 Toshiyuki Yasui,5 Kunihiko Hayashi3 1Department of Obstetrics and Gynecology, Niigata City General Hospital, Niigata, Japan; 2Gunma University Center for Mathematics and Data Science, Maebashi, Gunma, Japan; 3Department of International/Community Health Laboratory Sciences, Graduate School of Health Sciences, Gunma University, Maebashi, Gunma, Japan; 4Department of Obstetrics and Gynecology, Tokyo Dental College Ichikawa General Hospital, Chiba, Japan; 5Department of Reproductive and Menopausal Medicine, Institute of Biomedical Science, Tokushima University Graduate School, Tokushima, JapanCorrespondence: Takumi KurabayashiDepartment of Obstetrics & Gynecology, Niigata City General Hospital, 463-7, Shumoku, Chuo-ku, Niigata City, Niigata Prefecture, 950-1197, JapanTel +81-25-281-5151Fax +81-25-281-5169Email takumi@hosp.niigata.niigata.jpPurpose: Although the validity of self-reported osteoporosis is often questioned, validation studies are lacking. This study was performed to investigate how well self-reported diagnoses of osteoporosis agreed with validated clinical information in young and middle-aged women in the Japan Nurses’ Health Study (JNHS), a nationwide prospective cohort study of nursing professionals.Patients and Methods: Data were reviewed for 15,717 subjects from the combined cohorts of the JNHS and a preceding pilot study (Gunma Nurses’ Health Study). The subjects’ mean age at the baseline (BL) survey was 41.6 ± 8.3 years, and the mean follow-up period was 11.5 ± 4.4 years. Participating nurses were mailed a follow-up questionnaire every 2 years. Respondents who self-reported a positive osteoporosis diagnosis during the study period were sent an additional confirmation questionnaire to corroborate the details.Results: The number (proportion) of women with osteoporosis was 884 (5.6%) [primary osteoporosis, 812 (5.2%); secondary osteoporosis, 72 (0.5%)]. The cumulative incidence of osteoporosis at the age of 40, 50, 60, 70, and 80 years was estimated to be 0.1% (95% confidence interval, 0.1– 0.2), 1.1% (0.9– 1.3), 7.7% (7.0– 8.4), 23.6% (21.6– 25.7), and 54.2% (40.2– 68.1), respectively. For BL and regular follow-up + expert review versus BL and regular follow-up + confirmation questionnaire + expert review, the positive predictive value (PPV) was 61.3% versus 85.6% and the negative predictive value (NPV) was 98.9% versus 98.2%, respectively.Conclusion: Self-reporting was associated with a high NPV for the incidence of osteoporosis. Although the PPV was slightly lower, additional corroborations by confirmation questionnaire might improve the PPV.Keywords: validation, self-reported diagnosis, osteoporosis, prospective cohort study, Japan Nurses’ Health Study

AIM The aim is to examine the prevalence of low bone mineral density (BMD) (osteoporosis and osteopenia) of lumbar and femoral bones in puerperal women for the prenatal and postnatal care to ensure their optimal bone health. METHODS We analyzed the first scan data of 1079 Japanese puerperal women without bone fracture (mean age 33.5 ± 4.5 years) who had undergone deliveries at Niigata City General Hospital for 10 years. We measured BMDs of the lumbar spine [LS], femoral neck [FN], and total hip [TH] with dual-energy X-ray absorptiometry (DXA) within 30 days after delivery. RESULTS The rates of osteoporosis of LS, FN, TH, and comprehensive diagnosis (CD) were 0.6%, 4.8%, 1.5%, and 5.4%, respectively, and osteopenia were 20.2%, 39.5%, 29.3%, and 44.3%, respectively. The multivariable-adjusted odds ratio (OR) for body mass index (BMI) before pregnancy reflected significant decreases in risk for low BMD with an OR of 0.78 (95% CI: 0.74-0.82) with the 1 kg/m2 increases. In lean women (BMI

In this study, we aimed to investigate the prevalence and factors associated with urinary symptoms using cross-sectional data from the Japan Nurses' Health Study, a prospective cohort study among female nurses.A total of 12,198 women were included. We calculated the prevalence of urinary symptoms. Odds ratios with 95% confidence intervals were estimated to determine the odds for overactive bladder (OAB), stress urinary incontinence, and mixed urinary incontinence.The mean age and body mass index (standard deviation, range) were 46.5 (±8.1, 27-82) years and 22.1 (±3.1, 12.9-44.6) kg/m2, respectively. The prevalence of OAB was 9.5% (OAB with urinary incontinence [-wet]: 5.4%, OAB without urinary incontinence: 4.1%), that of stress urinary incontinence (without OAB-wet) was 13.9%, and that of mixed urinary incontinence was 2.1%. Multivariable-adjusted logistic regression analysis showed a significant association between OAB and age 45 to 54 years, and postmenopausal status was moderately associated with OAB in that analysis. In the multivariable-adjusted model, age groups 45 to 49 and 50 to 54 years, body mass index 23-27.4 and ≥ 27.5 kg/m2, and parous status were significantly associated with stress urinary incontinence (without OAB-wet).This study showed a significant association of OAB with ages 45 to 54 years and postmenopausal status. Further studies should consider the association between time since menopause and OAB symptoms in the perimenopausal period. A high body mass index and parous status are strongly associated with stress urinary incontinence, and stress urinary incontinence symptoms may become less frequent after menopause.Video Summary:http://links.lww.com/MENO/A853.

Objective We aimed to investigate whether hypertensive disorders of pregnancy are associated with problematic hot flashes in Japanese women. Methods In this study, we included participants in the Japan Nurses' Health Study who were women aged 41 to 55 years at baseline, parous, and complete a 4-year follow-up questionnaire. The main outcome was self-reported problematic hot flashes. At the 4-year follow-up survey, we investigated hot flashes using the Climacteric Symptom Checklist for Japanese Women, which was developed by a subcommittee of the Japan Society of Obstetrics and Gynecology. Results At the baseline survey, of the 4,627 women included in the analysis, 610 (13.2%) reported a history of hypertensive disorders of pregnancy. At the 4-year follow-up survey, 394 women (8.5%) reported problematic hot flashes, 529 (11.4%) were diagnosed with premenopausal hypertension, and 2,389 (51.5%) were postmenopausal. Multivariable logistic regression analysis revealed a multivariable-adjusted odds ratio (95% confidence interval) of problematic hot flashes for women with a history of hypertensive disorders of pregnancy of 1.42 (1.04-1.94), compared with women without this history. Among women without premenopausal hypertension, the odds ratio increased to 1.55 (1.10-2.19) among women with hypertensive disorders of pregnancy as compared with those without these disorders. Conclusions In this prospective study, we found that women with a history of hypertensive disorders of pregnancy have a significantly increased risk of problematic hot flashes, compared with their counterparts without a history of hypertensive disorders of pregnancy.

Background Many women experience various symptoms during the period of menopausal transition, including complaints of reduced cognitive functioning. However, these complaints are not necessarily recognized as core menopausal symptoms. In this study, we sought to characterize subjective complaints of reduced cognitive functioning by analyzing cross-sectional data from the Japan Nurses’ Health Study (JNHS). Methods The JNHS 4-year follow-up questionnaire containing a 21-item climacteric symptom checklist, which included a question about “poor memory or forgetfulness”, was mailed between 2005 and 2011 to all JNHS participants, regardless of their age at the time of the survey. We estimated the prevalence of slight and severe complaints in 5-year age-groups. We used principal component analysis to explore the underlying factors among the 21 symptoms during the menopausal transition period in women aged 45–54 years at the time of the survey. We also examined risk factors for complaints using multivariable modified Poisson regression analysis. Results In total, 12,507 women responded to the 4-year survey. The mean age at the time of the 4-year survey was 46.5 years (range 27–82). “Poor memory or forgetfulness” showed a peak prevalence of 81.7% (severe 27.9%; slight 53.8%) at 50–54 years, and gradually decreased after 55 years. Principal component analysis indicated that “poor memory or forgetfulness” belonged to somatic symptoms and was close to psychological symptoms in women aged 45–54 years. In women aged 45–54 years, the complaint was also significantly associated with hot flashes and sweats. Multivariable modified Poisson regression analysis showed that menopausal status (uncertain and postmenopausal), less sleep (sleep of Conclusions We found that prevalence of “poor memory or forgetfulness” was highest during the menopausal transition period and among perimenopausal women. This subjective complaint was associated with somatic, psychological complaints and VMS. It may be useful for women with cognitive problems in the transition period to consider management of comorbid menopausal symptoms.

Objective We aimed to establish correlations for the levels of follicle-stimulating hormone (FSH), estrone (E1) and estradiol (E2) between urine and serum in premenopausal and postmenopausal women using immunoassays. Methods In this study of 92 women (61 postmenopausal, 31 premenopausal), both urine and blood specimens were collected on the same day and stored at 4 °C for analysis by chemiluminescent immunoassay, radioimmunoassay and/or electrochemiluminescent immunoassay. Results There were correlations in the levels of FSH, E1 and E2 between urine and serum in both postmenopausal (r = 0.96 for FSH, r = 0.91 for E1, r = 0.80 for E2) and premenopausal (r = 0.98 for FSH, r = 0.92 for E1, r = 0.90 for E2) women. It is indicated that the correlations were stronger in the premenopausal group compared with the postmenopausal group, especially for FSH. Conclusion The levels of FSH, E1 and E2 in urine correlated with those in the serum in premenopausal and postmenopausal women. Urine samples could be used instead of serum samples to measure hormone levels, which would reduce the difficulty of conducting large survey studies.

The Japan Nurses' Health Study (JNHS) is a large-scale, nationwide prospective cohort study of female nurses. This study aimed to examine the validity of self-reported diagnosis of cancer among the JNHS cohort members (N=15,019).For women who reported any diagnosis of five cancers (stomach, colorectal, liver, lung and thyroid) in the biennial follow-up surveys, an additional outcome survey, medical facility survey, and confirmation of death certificate (DC) were conducted. The JNHS Validation Study Committee (referred to as "the committee") made a final decision on the reported outcomes. To examine the validity of self-reported diagnosis of cancer, the positive predictive value (PPV) was calculated using the committee's decision as the gold standard. To examine the validity of the committee's decision based on self-reports and DCs, PPV was calculated using physician-reported information as the gold standard.The PPV of self-reported diagnosis in the biennial follow-up surveys was 77.8% for stomach, 66.2% for colorectal, 41.7% for liver, 60.2% for lung, and 64.6% for thyroid cancer. The corresponding PPVs in the additional outcome survey were 96.2%, 80.7%, 62.5%, 82.5%, and 96.9%, respectively. The PPV of the committee's decision was 100% for stomach, 87.5% for colorectal, 94.7% for lung, and 100% for thyroid cancer (data not available for liver cancer). The proportion of DC-only cases among committee-defined cases was below 10% for all cancers except liver cancer (28.6%).The validity of identifying cancer diagnosis based on self-reported information in the JNHS was favorable for stomach, colorectal, lung and thyroid cancer.

Single-nucleotide polymorphisms (SNPs) of the IDO1 and IDO2 genes have been associated with some diseases. Here, we investigated the association of IDO1 and IDO2 SNPs with the susceptibility to multiple myeloma (MM) and their relationships with MM clinical features. We obtained genomic DNA from 100 patients with MM and 149 healthy race-matched controls and determined IDO1 promoter - 1849G/T (rs3824259) and IDO2 R248W (rs10109853) genotypes by using the polymerase chain reaction-restriction fragment length polymorphism method. The patients with MM had a significantly higher frequency of the IDO2 R248W RR genotype (high-activity type) (59.0% vs. 43.6%, odds ratio = 1.86, 95% confidence interval = 1.11-3.11, P = 0.017) compared with those in healthy controls. Patients with the IDO2 R248W RR genotype (high-activity type) were significantly younger and had a significantly lower frequency of International Staging System (ISS) stage III condition than those with the RW and WW genotypes (median 63 years vs. 69 years, P = 0.025; 15 [25.4%] vs. 50 [48.8%]). In addition, the IDO2 R248W RR genotype was significantly associated with a higher level of hemoglobin at diagnosis (mean ± standard deviation, 10.7 ± 2.36 vs. 9.27 ± 2.40 g/dL; P = 0.0032). Neither polymorphism significantly affected overall survival. Our study indicates that IDO2 R248W may be associated with the susceptibility to MM and severity of anemia.

Background Face-to-face individual cognitive behavioral therapy (CBT) and internet-based CBT (ICBT) without videoconferencing are known to have long-term effectiveness for obsessive-compulsive disorder (OCD), panic disorder (PD), and social anxiety disorder (SAD). However, videoconference-delivered CBT (VCBT) has not been investigated regarding its long-term effectiveness and cost-effectiveness. Objective The purpose of this study was to investigate the long-term effectiveness and cost-effectiveness of VCBT for patients with OCD, PD, or SAD in Japan via a 1-year follow-up to our previous 16-week single-arm study. Methods Written informed consent was obtained from 25 of 29 eligible patients with OCD, PD, and SAD who had completed VCBT in our clinical trial. Participants were assessed at baseline, end of treatment, and at the follow-up end points of 3, 6, and 12 months. Outcomes were the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Panic Disorder Severity Scale (PDSS), Liebowitz Social Anxiety Scale (LSAS), Patient Health Questionnaire–9 (PHQ-9), General Anxiety Disorder–7 (GAD-7), and EuroQol-5D-5L (EQ-5D-5L). To analyze long-term effectiveness, we used mixed-model analysis of variance. To analyze cost-effectiveness, we employed relevant public data and derived data on VCBT implementation costs from Japanese national health insurance data. Results Four males and 21 females with an average age of 35.1 (SD 8.6) years participated in the 1-year follow-up study. Principal diagnoses were OCD (n=10), PD (n=7), and SAD (n=8). The change at 12 months on the Y-BOCS was −4.1 (F1=4.45, P=.04), the change in PDSS was −4.4 (F1=6.83, P=.001), and the change in LSAS was −30.9 (F1=6.73, P=.01). The change in the PHQ-9 at 12 months was −2.7 (F1=7.72, P=.007), and the change in the GAD-7 was −3.0 (F1=7.09, P=.009). QALY at 12 months was 0.7469 (SE 0.0353, 95% Cl 0.6728-0.821), and the change was a significant increase of 0.0379 (P=.01). Total costs to provide the VCBT were ¥60,800 to ¥81,960 per patient. The set threshold was ¥189,500 ($1723, €1579, and £1354) calculated based on willingness to pay in Japan. Conclusions VCBT was a cost-effective way to effectively treat Japanese patients with OCD, PD, or SAD. Trial Registration University Hospital Medical Information Network Clinical Trials Registry UMIN000026609; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030495

Objective We previously reported that hypertensive disorder of pregnancy (HDP) was a risk factor for hypertension and hypercholesterolemia in later life. Additionally, the age-adjusted odds ratio (OR) of HDP was 2.72 for Japanese women whose mothers had a history of HDP versus those whose mothers did not. This study aimed to clarify the association of HDP with birth weight and gestational age. Study Design A self-administered baseline survey of the Japanese Nurses' Health Study (JNHS) cohort was conducted from 2001 to 2007. Data on 17,278 parous female nurses who knew their own birth weights were extracted from the JNHS baseline survey (n = 49,927) and subjected to cross-sectional, retrospective analysis. Data on weeks of gestation, birth weight, and history of HDP were collected. Results The age-adjusted ORs for HDP were 1.62 (95% confidence interval [CI]: 1.20–2.19) for birth weight Conclusion Among women in Japan, a history of low birth weight and prematurity are risk factors for HDP in later life. The risk of HDP among women born with low birth weight and/or premature deserves attention.

This randomized, double-blind, placebo-controlled trial evaluated dexamethasone efficacy at preventing fever, anorexia, and nausea/vomiting, the most frequent adverse events of transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Child-Pugh class A/B patients with HCC and no macrovascular invasion/extrahepatic metastases were randomly assigned to either a dexamethasone regimen (day 1, intravenous dexamethasone [20 mg] and granisetron [3 mg] before TACE; days 2 and 3, intravenous dexamethasone [8 mg]) or a control regimen (day 1, intravenous placebo [saline] and granisetron [3 mg]; days 2 and 3, intravenous placebo). The primary endpoint was complete response, defined as the absence of grade ≥1 fever, anorexia, or nausea/vomiting according to the Common Terminology Criteria for Adverse Events (version 4.0) and no use of rescue therapy for 120 hours after TACE. A total of 120 patients between October 2010 and June 2013 were randomly assigned to treatment groups. Overall the complete response rate was greater with the dexamethasone regimen than with the control regimen (47.5%, 95% confidence interval 34.3%-60.9%, versus 10.2%, 95% confidence interval 3.8%-20.8%; P < 0.001). Cumulative incidences of fever, anorexia, and nausea/vomiting were higher in the control regimen group compared with the dexamethasone group (P < 0.001, P < 0.001, and P = 0.095, respectively). The dexamethasone regimen was generally well tolerated by HCC patients including those with well-controlled diabetes mellitus and those with hepatitis B virus infection. Conclusion: The dexamethasone regimen was more effective than the control regimen at preventing TACE-induced fever, anorexia, and nausea/vomiting in patients with HCC. (Hepatology 2018;67:575-585).

BACKGROUND Face-to-face individual cognitive behavioral therapy (CBT) and internet-based CBT (ICBT) without videoconferencing are known to have long-term effectiveness for obsessive-compulsive disorder (OCD), panic disorder (PD), and social anxiety disorder (SAD). However, videoconference-delivered CBT (VCBT) has not been investigated regarding its long-term effectiveness and cost-effectiveness. OBJECTIVE The purpose of this study was to investigate the long-term effectiveness and cost-effectiveness of VCBT for patients with OCD, PD, or SAD in Japan via a 1-year follow-up to our previous 16-week single-arm study. METHODS Written informed consent was obtained from 25 of 29 eligible patients with OCD, PD, and SAD who had completed VCBT in our clinical trial. Participants were assessed at baseline, end of treatment, and at the follow-up end points of 3, 6, and 12 months. Outcomes were the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Panic Disorder Severity Scale (PDSS), Liebowitz Social Anxiety Scale (LSAS), Patient Health Questionnaire–9 (PHQ-9), General Anxiety Disorder–7 (GAD-7), and EuroQol-5D-5L (EQ-5D-5L). To analyze long-term effectiveness, we used mixed-model analysis of variance. To analyze cost-effectiveness, we employed relevant public data and derived data on VCBT implementation costs from Japanese national health insurance data. RESULTS Four males and 21 females with an average age of 35.1 (SD 8.6) years participated in the 1-year follow-up study. Principal diagnoses were OCD (n=10), PD (n=7), and SAD (n=8). The change at 12 months on the Y-BOCS was −4.1 (F1=4.45, P=.04), the change in PDSS was −4.4 (F1=6.83, P=.001), and the change in LSAS was −30.9 (F1=6.73, P=.01). The change in the PHQ-9 at 12 months was −2.7 (F1=7.72, P=.007), and the change in the GAD-7 was −3.0 (F1=7.09, P=.009). QALY at 12 months was 0.7469 (SE 0.0353, 95% Cl 0.6728-0.821), and the change was a significant increase of 0.0379 (P=.01). Total costs to provide the VCBT were ¥60,800 to ¥81,960 per patient. The set threshold was ¥189,500 ($1723, €1579, and £1354) calculated based on willingness to pay in Japan. CONCLUSIONS VCBT was a cost-effective way to effectively treat Japanese patients with OCD, PD, or SAD. CLINICALTRIAL University Hospital Medical Information Network Clinical Trials Registry UMIN000026609; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030495

Soluble CD14 (sCD14) is one of the immunomodulatory factors in breast milk (BM). Although it may be involved in the prevention of atopic symptoms and sensitization to both food and inhalant allergens, conflicting evidence exists concerning its protective effects. In this study, we investigated the relationship between sCD14 in colostrum and 1-month BM, and the development of atopic dermatitis (AD) and sensitization to food and aeroallergens at 9 months of age in infants who were exclusively or almost exclusively breastfed up to 4 months of age. BM samples were collected from lactating mothers who participated in a 2 &times, 2 factorial, randomized, nontreatment controlled trial study set in Tokyo, which looked at the efficacy of emollients and synbiotics in preventing AD and food allergy in children during the first year of life. A total of 258 colostrum samples and 269 1-month BM samples were analyzed. We found that one-month BM sCD14 levels in the AD group were significantly lower than in the non-AD group. Levels of sCD14 in 1-month BM were not related to allergen sensitization in the overall analysis, but egg white sensitization correlated inversely with 1-month BM sCD14 in infants without AD. The results suggest that sCD14 in BM may be involved in atopic manifestations in early infancy.

Background: Atopic dermatitis (AD) and food allergy (FA) are common childhood diseases, which may either be interrelated or be the result of skin barrier disruption and gut mucosal dysbiosis. Although some evidence suggests the efficacy of emollients and synbiotics, there is no conclusive evidence on the use of these interventions alone or in combination. Objectives: This study is aimed at identifying the efficacy of emollients and synbiotics in preventing AD and FA in children during the first year of life. Methods: The babies of mothers recruited prenatally received either an emollient, synbiotic, both or neither. The intervention was carried out from birth up to 6 months of age. The age of occurrence of AD and FA were reported in multiple questionnaires at 1, 6, and 9 months and at 1 year of age. AD was diagnosed by a pediatrician at 9 months of age. Results: A ­total of 459 babies qualified for the outcome assessment at 1 year of age. Neither the emollient nor the synbiotic showed any effect on reducing the development of AD and FA at 1 year of age. Conclusions: This study did not provide any evidence to show that emollients and synbiotics, alone or in combination are sufficient to prevent the occurrence of AD or FA in children up to 1 year of age.

Fundamento: uma boa condição dos tecidos moles é necessária para a longevidade de tratamentos com implantes dentários. Os tecidos moles periimplantares são semelhantes ao periodonto de proteção, sendo importante para oferecer uma barreira contra a agressão bacteriana ao tecido ósseo. Objetivo: o objetivo foi realizar uma revisão de literatura sobre a importância da mucosa queratinizada na implantodontia; analisando a relação entre a manutenção gengival e saúde periimplantar. Metodologia: bases de dados foram acessadas para realização da pesquisa de artigos publicados na literatura Odontológica, na língua portuguesa e inglesa, principalmente entre os anos de 2010 a 2019. As bases de dados acessadas foram: LILACS, PUBMED, Scielo e a Biblioteca Digital Brasileira de Teses e Dissertações (BDTD). As palavras chaves usadas foram: osseointegration AND periodontics AND mouth mucosa AND gingiva. Discussão: vários estudos, desde estudos animais à revisões sistemáticas de literatura foram realizadas para avaliar o papel do tecido ceratinizado na implantodotia, e observaram que este tecido atua positivamente, com melhora do selamento periimplantar, redução de inflamação local, melhora na realização da higiene local e menos casos de recessão tecidual. Conclusão: conclui-se que o tecido ceratinizado é fundamental para a saúde periimplantar, atuando tanto na saúde oral do paciente reabilitado, quanto na sua estética e funcionalidade.

BACKGROUND In reality, pharmacotherapy still remains the most common treatment for insomnia. OBJECTIVE This study aimed to examine the effectiveness of our internet-delivered computerized cognitive behavioral therapy (ICBT) program as an adjunct to usual care (UC) compared with UC alone in patients with insomnia who remain symptomatic following hypnotics. METHODS We recruited 23 patients with insomnia who remained symptomatic following pharmacologic treatment including benzodiazepines, and we conducted an exploratory randomized controlled trial. The primary outcome was the Pittsburgh Sleep Quality Index (PSQI) at week 6 of the treatment. Secondary outcomes were sleep onset latency, total sleep time, sleep efficiency, number of awakenings, refreshment and soundness of sleep, anxiety by Hospital Anxiety and Depression Scale, depression measured by the Center for Epidemiologic Studies Depression Scale, and quality of life (QOL) measured by the EuroQol-5D. All parameters were measured at weeks 0 (baseline), 6 (postintervention), and 12 (follow-up). RESULTS The adjusted mean reduction (−6.11) in PSQI at week 6 from baseline in the ICBT plus UC group was significantly (P CONCLUSIONS These results indicated that our 6-week ICBT program is an effective treatment adjunct to UC for improving insomnia and related symptoms even after unsuccessful pharmacotherapy. CLINICALTRIAL University Hospital Medical Information Network Clinical Trials Registry: UMIN000021509; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023545 (Archived by WebCite at http://www.webcitation. org/75tCmwnYt).

BACKGROUND Cognitive behavioral therapy (CBT) is the first-line treatment for adults with obsessive-compulsive disorder (OCD), panic disorder (PD), and social anxiety disorder (SAD). Patients in rural areas can access CBT via the internet. The effectiveness of internet-delivered cognitive behavioral therapy (ICBT) has been consistently shown, but no clinical studies have demonstrated the feasibility of ICBT with real-time therapist support via videoconference for OCD, PD, and SAD at the same time. OBJECTIVES This study aimed to evaluate the feasibility of videoconference-delivered CBT for patients with OCD, PD, or SAD. METHODS A total of 30 Japanese participants (mean age 35.4 years, SD 9.2) with OCD, SAD, or PD received 16 sessions of individualized videoconference-delivered CBT with real-time support of a therapist, using tablet personal computer (Apple iPad Mini 2). Treatment involved individualized CBT formulations specific to the presenting diagnosis; all sessions were provided by the same therapist. The primary outcomes were reduction in symptomatology, using the Yale-Brown obsessive-compulsive scale (Y-BOCS) for OCD, Panic Disorder Severity Scale (PDSS) for PD, and Liebowitz Social Anxiety Scale (LSAS) for SAD. The secondary outcomes included the EuroQol-5 Dimension (EQ-5D) for Quality of Life, the Patient Health Questionnaire (PHQ-9) for depression, the Generalized Anxiety Disorder (GAD-7) questionnaire for anxiety, and Working Alliance Inventory-Short Form (WAI-SF). All primary outcomes were assessed at baseline and at weeks 1 (baseline), 8 (midintervention), and 16 (postintervention) face-to-face during therapy. The occurrence of adverse events was observed after each session. For the primary analysis comparing between pre- and posttreatments, the participants’ points and 95% CIs were estimated by the paired t tests with the change between pre- and posttreatment. RESULTS A significant reduction in symptom of obsession-compulsion (Y-BOCS=−6.2; Cohen d=0.74; 95% CI −9.4 to −3.0, P=.002), panic (PDSS=−5.6; Cohen d=0.89; 95% CI −9.83 to −1.37; P=.02), social anxiety (LSAS=−33.6; Cohen d=1.10; 95% CI −59.62 to −7.49, P=.02) were observed. In addition, depression (PHQ-9=−1.72; Cohen d=0.27; 95% CI −3.26 to −0.19; P=.03) and general anxiety (GAD-7=−3.03; Cohen d=0.61; 95% CI −4.57 to −1.49, P CONCLUSIONS Videoconference-delivered CBT for patients with OCD, SAD, and SAD may be feasible and acceptable.

Background: The prevalence and risk factors for endometriosis may differ according to diagnosis methodologies,such as study populations and diagnostic accuracy. We examined risk profiles in imaging-diagnosed endometriosiswith and without surgical confirmation in a large population of Japanese women, as well as the differences in riskprofiles of endometriosis based on history of infertility.Methods: Questionnaires that included items on sites of endometriosis determined by imaging techniques andsurgical procedure were mailed to 1025 women who self-reported endometriosis in a baseline survey of the JapanNurses’ Health Study (n = 15019).Results: Two hundred and ten women had surgically confirmed endometriosis (Group A), 120 had imaging-diagnosed endometriosis without a surgical procedure (Group B), and 264 had adenomyosis (Group C). A shortmenstrual cycle at 18–22 years of age and cigarette smoking at 30 years of age were associated with significantlyincreased risk of endometriosis (Group A plus Group B), while older age was associated with risk of adenomyosis(Group C). In women with a history of infertility, a short menstrual cycle was associated with a significantlyincreased risk of endometriosis in both Group A and Group B, but risk profiles of endometriosis were differentbetween Group A and Group B in women without a history of infertility.Conclusions: Women with surgically confirmed endometriosis and those with imaging-diagnosed endometriosiswithout surgery have basically common risk profiles, but these risk profiles are different from those withadenomyosis. The presence of a history of infertility should be taken into consideration for evaluation of risk profiles.Key words: endometriosis; risk factors; validation

Background There is still no definite treatment for refractory Kawasaki disease (KD). In this pilot study, we evaluated the safety and efficacy of a new protocol consisting of sivelestat sodium hydrate (SSH) combined with additional i.v. immunoglobulin (IVIG) for KD resistant to initial IVIG therapy. Methods This study is a prospective non-randomized, open-label and single-arm study undertaken in a population of refractory KD patients at Chiba University Hospital from December 2006 to March 2016. The subjects had KD resistant to initial IVIG (2 g/kg) and received SSH (0.2 mg/kg/h for 5 days) combined with additional IVIG (2 g/kg) as a second-line therapy. We evaluated the safety and efficacy of the treatment during the study period. Results Forty-six KD patients were enrolled in this study and no serious adverse event was noted. Of these, 45 patients were evaluated for the incidence of coronary artery lesions, which occurred in one patient (2.2%; 95% CI: 0.5-15.2). Twenty-eight (62.2%) responded promptly and were afebrile after the therapy. The median total duration of fever was 8 days (range, 6-28 days). Conclusions Additional IVIG combined with SSH as a second-line therapy for KD refractory to initial IVIG therapy was safe and well tolerated and could be a promising option for severe KD. Further investigations are expected to clarify the safety and timing of SSH treatment for KD.

Objective To clarify the associations between pregnancy-induced hypertension (PIH) with heritability of PIH from mother to daughter and the risk of cardiovascular disease in later life in Japanese women. Study design The Japan Nurses’ Health Study (JNHS) is a cohort study of Japanese women's health. Data from the JNHS baseline survey between 2001 and 2007 were used to conduct a cross-sectional analysis. Of the 49,927 respondents in the baseline survey, 10,456 parous women who were ≥45 years old at baseline were included in the analysis. Main outcome measures The age-adjusted odds ratio (OR) of PIH in women whose mother had a history of PIH, and the age-adjusted OR of PIH in participants for hypertension, hypercholesterolemia and diabetes mellitus (DM). Results The age-adjusted OR of PIH was 2.72 (95% confidence interval [CI]: 2.14–3.46) in women whose mother had a history of PIH compared with those whose mother did not have PIH. PIH was a risk factor for hypertension (age adjusted OR: 2.85, 95% CI: 2.45–3.11), hypercholesterolemia (age-adjusted OR: 1.49, 95% CI: 1.29–1.72) and DM (age-adjusted OR: 1.53, 95% CI: 1.11–2.11), as determined by logistic regression analysis. Conclusions In Japanese women, the risk of PIH is approximately 2.7-fold greater in those whose mothers also had PIH compared with those whose mothers did not. PIH is a risk factor for hypertension, hypercholesterolemia, and diabetes mellitus in later life.

Background Cognitive behavioral therapy (CBT) is the first-line treatment for adults with obsessive-compulsive disorder (OCD), panic disorder (PD), and social anxiety disorder (SAD). Patients in rural areas can access CBT via the internet. The effectiveness of internet-delivered cognitive behavioral therapy (ICBT) has been consistently shown, but no clinical studies have demonstrated the feasibility of ICBT with real-time therapist support via videoconference for OCD, PD, and SAD at the same time. Objectives This study aimed to evaluate the feasibility of videoconference-delivered CBT for patients with OCD, PD, or SAD. Methods A total of 30 Japanese participants (mean age 35.4 years, SD 9.2) with OCD, SAD, or PD received 16 sessions of individualized videoconference-delivered CBT with real-time support of a therapist, using tablet personal computer (Apple iPad Mini 2). Treatment involved individualized CBT formulations specific to the presenting diagnosis; all sessions were provided by the same therapist. The primary outcomes were reduction in symptomatology, using the Yale-Brown obsessive-compulsive scale (Y-BOCS) for OCD, Panic Disorder Severity Scale (PDSS) for PD, and Liebowitz Social Anxiety Scale (LSAS) for SAD. The secondary outcomes included the EuroQol-5 Dimension (EQ-5D) for Quality of Life, the Patient Health Questionnaire (PHQ-9) for depression, the Generalized Anxiety Disorder (GAD-7) questionnaire for anxiety, and Working Alliance Inventory-Short Form (WAI-SF). All primary outcomes were assessed at baseline and at weeks 1 (baseline), 8 (midintervention), and 16 (postintervention) face-to-face during therapy. The occurrence of adverse events was observed after each session. For the primary analysis comparing between pre- and posttreatments, the participants’ points and 95% CIs were estimated by the paired t tests with the change between pre- and posttreatment. Results A significant reduction in symptom of obsession-compulsion (Y-BOCS=−6.2; Cohen d=0.74; 95% CI −9.4 to −3.0, P=.002), panic (PDSS=−5.6; Cohen d=0.89; 95% CI −9.83 to −1.37; P=.02), social anxiety (LSAS=−33.6; Cohen d=1.10; 95% CI −59.62 to −7.49, P=.02) were observed. In addition, depression (PHQ-9=−1.72; Cohen d=0.27; 95% CI −3.26 to −0.19; P=.03) and general anxiety (GAD-7=−3.03; Cohen d=0.61; 95% CI −4.57 to −1.49, P

4071Background: Fever, nausea, vomiting, and anorexia are the most frequent adverse events of transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). In thi...

Objective To classify diseases based on age at peak incidence to identify risk factors for later disease in women9s life course. Design A cross-sectional baseline survey of participants in the Japan Nurses’ Health Study. Setting A nationwide prospective cohort study on the health of Japanese nurses. The baseline survey was conducted between 2001 and 2007 (n=49 927). Main outcome measures Age at peak incidence for 20 diseases from a survey of Japanese women was estimated using the Kaplan-Meier method with the Kernel smoothing technique. The incidence rate and peak incidence for diseases whose peak incidence occurred before the age of 45 years or before the perimenopausal period were selected as early-onset diseases. The OR and 95% CI were estimated to examine the risk of comorbidity between early-onset and other diseases. Results Four early-onset diseases (endometriosis, anaemia, migraine headache and uterine myoma) were significantly correlated with one another. Late-onset diseases significantly associated (OR>2) with early-onset diseases included comorbid endometriosis with ovarian cancer (3.65 (2.16 to 6.19)), endometrial cancer (2.40 (1.14 to 5.04)) and cerebral infarction (2.10 (1.15 to 3.85)); comorbid anaemia with gastric cancer (3.69 (2.68 to 5.08)); comorbid migraine with transient ischaemic attack (3.06 (2.29 to 4.09)), osteoporosis (2.11 (1.71 to 2.62)), cerebral infarction (2.04 (1.26 to 3.30)) and angina pectoris (2.00 (1.49 to 2.67)); and comorbid uterine myoma with colorectal cancer (2.31 (1.48 to 3.61)). Conclusions While there were significant associations between four early-onset diseases, women with a history of one or more of the early-onset diseases had a higher risk of other diseases later in their life course. Understanding the history of early-onset diseases in women may help reduce the subsequent risk of chronic diseases in later life.

Objective To examine the effects of stamped reply envelope and the timing of newsletter distribution. Design A randomised controlled trial in a prospective cohort study with a 2×2 factorial design of two interventions. Setting The Japan Nurses’ Health Study (JNHS), a prospective cohort study for women9s health. Participants The present study included 6938 women who were part of the first-year entry cohort for the fifth wave of the biannual follow-up survey of the JNHS. Intervention The participants were randomly allocated into four groups; Group-1 (business-reply, newsletter with initial mailing), Group-2 (business-reply, newsletter with reminder), Group-3 (stamped envelopes, newsletter with initial mailing) and Group-4 (stamped envelopes, newsletter with reminder). The thank-you and reminder letters were mailed out at the end of the sixth week. This study was censored at the end of 12 weeks. Main outcome measures Main outcome measures were cumulative response at the end of 6 and 12 weeks after mailing out the questionnaire. Results The cumulative response at 12 weeks were 58.3% for Group-1, 54.1% for Group-2, 60.5% for Group-3 and 56.7% for Group-4 (p=0.001). The odds of the response was higher for stamped envelopes than for business-reply envelopes (OR (95% CI)=1.10(1.00 to 1.21)). The odds was higher for newsletter delivery with initial mailing than for with reminder (1.18(1.07 to 1.29)). The response in first 6 weeks for stamped envelope was significantly higher than for business-reply envelope (p=0.047). Although the response in 6 weeks for women received the newsletter with initial mailing was lower than for women who did not, the proportions did not differ significantly (p=0.291). Conclusions The style of return envelope affected response rates of mail survey. The results of this study suggest that practices of provision of the additional information, should be handled individually in advance, as a separate event from sending follow-up questionnaire or reminder letters.

Using in vivo and in vitro experimental models, the uptake and excretion of 67Ga-citrate in tumor cells and normal cells were studied. The time-lapse accumulation of 67Ga in the tumor of rats bearing Yoshida sarcoma reached its peak 24 h after the administration of 67Ga and gradually decreased thereafter. However, the excretion of 67Ga from the tumor was less than that from normal lung. For culture cells in vitro, the uptake of 67Ga increased with lapse of contact time between 67Ga and the cells, but there was no distinct difference between the results for tumor cells and normal skin fibroblasts. The excretion of 67Ga from the cells tended to decrease with prolongation of the contact time, the excretion from tumor cells being only about 10% after a contact time of 24 h. This indicated a significant delay in excretion in comparison with that of normal skin fibroblasts. This delay in the excretion of 67Ga may be an important factor in the tumor accumulation of 67Ga.

The degree of deposition of small-particle colloids such as 99mTc-antimony sulfide colloids (ASC-group) and 99mTc-rhenium colloid (Tc-Re) in the bone marrow and lymph node was studied. H-ASC that was prepared in our laboratory was concentrated to a higher degree both in the bone marrow and lymph nodes, compared with other colloids. The H-ASC were mostly from 5 to 12.5 nm and the shape was uniform and spherical. The degree of deposition of Tc-Re in rabbit lymph nodes was not higher, however, the label was considered to be valuable clinically. The degree of deposition of Tc-Re in the bone marrow was not satisfactory. The size of Tc-Re was much smaller than H-ASC, ranging from 3 to 5 nm. From these results, it is considered that factors affecting deposition in the marrow are not identical to those in the lymph nodes.

This report is a study of the differential diagnosis of bone diseases using nucleomedical procedures. Experimental and clinical studies on the accumulation of 201Tl and 67Ga in bone inflammation and bone tumors were performed. Also, the degree of deposition of 99mTc-phosphorous compounds represented as a color difference was evaluated for a differentiation between malignant and benign diseases of the spine and shoulder. Uptake of 201Tl in inflammation of the spine and in tumor of the pelvis of rabbits was very low, while that of 67Ga was high. Uptake of 67Ga decreased gradually with lapse of time after the onset of inflammation. These experimental results agreed with clinical studies. The detectability of malignant tumors with 201Tl was inferior to that with 99mTc-label and 67Ga, although osteolytic lesions were occasionally 201Tl-positive. In terms of color range, the difference was 2 or less in spines of normal subjects and 3 or more in the metastatic bone disease and compression fracture. This difference was not statistically significant. Since 67Ga scan was occasionally negative in compression fracture, a differentiation was considered to be possible in such a case. A combined study of bone imaging with 99mTc-phosphorous compound including color difference, 67Ga imaging, bone-marrow imaging and radiography are considered to be helpful for the differentiation.

The effect of FeCl3 on 67Ga uptake by HeLa S3 cells was studied in vitro. Uptake of 67Ga by HeLa S3 cells was influenced by the concentrations of serum in the medium and especially that of transferrin added to the medium. Therefore, it is assumed that a mechanism of 67Ga uptake exists mediated by transferrin. However, when 10(-2)--10(-1) mM FeCl3 was added to the medium in the same experimental system, a remarkable increase of 67Ga uptake was noted. Results of equilibrium dialysis, showed that binding of 67Ga to transferrin was inhibited by the administration of FeCl3. Moreover, the formation of a complex of 67Ga and FeCl3, which did not pass through the cellulose membrane, was observed. A correlation was found between an increase in 67Ga uptake by HeLa S3 cells and the formation of the 67Ga--Fe complex. These results indicate that another mechanism of 67Ga accumulation, namely the formation of a 67Ga--Fe complex plays a role in the uptake of 67Ga by tumor cells in the presence of iron.

With 9 kinds of available 99mTc-colloid kits for RES imaging, especially from the aspect of RES imaging of the bone marrow, observations were conducted on pH, the presence of free 99mTcO4(-), labelling efficiency, rabbit blood clearance, the uptake in RES, urinary excretion, as well as the scintigraphy with rabbits and clinical cases. Compared to 198Au-colloid, marrow to liver ratio was found to be about the same, but its uptake to the spleen and liver was greater. In particular its urinary excretion was much more marked than 198Au-colloid, and in clinical use the bladder was more often delineated. This fact seems to suggest that it is desirable to develope a 99mTc-colloid more suitabale for the bone marrow scintigraphy.

Lymphoscintigraphy with SC injection of 67Ga-citrate was carried out on patients with lymph node metastasis and malignant lymphoma. The dose given at each injection site was about 200 muCi and scintigraphy was started about 5 min after injection. Metastatic lymph nodes and malignant lymphoma were successfully imaged. This positive delineation corresponded well to cold lesions detected by lymphoscintigraphy with 99mTc-rhenium colloid in metastatic lymph nodes. Hotter lesions in malignant lymphoma were scanned positively with 99mTc-rhenium colloid by this method. In in vitro studies, incorporation of 67Ga-citrate in HeLa S3 cells was about 4 times that in macrophages, when the incubation time was 1 h, while colloidal uptake by macrophages was 13 times that by HeLa S3 cells. The binding of 67Ga to transferrin in lymph and pinocytosis are suggested mechanisms of localization. A combination of colloid- and sc 67Ga-lymphoscintigraphy would be of value in the diagnosis of lymph node disease.