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Aims: We evaluated a self-care intervention with a novel mobile application (app) in chronic heart failure (HF) patients. To facilitate patient-centred care in HF management, we developed a self-care support mobile app to boost HF patients' optimal self-care., Methods and Results: We conducted a multicentre, randomized, controlled study evaluating the feasibility of the self-care support mobile app designed for use by HF patients. The app consists of a self-monitoring assistant, education, and automated alerts of possible worsening HF. The intervention group received a tablet personal computer (PC) with the self-care support app installed, and the control group received a HF diary. All patients performed self-monitoring at home for 2 months. Their self-care behaviours were evaluated by the European Heart Failure Self-Care Behaviour Scale. We enrolled 24 outpatients with chronic HF (ages 31-78 years; 6 women, 18 men) who had a history of HF hospitalization. During the 2 month study period, the intervention group ( n = 13) showed excellent adherence to the self-monitoring of each vital sign, with a median [interquartile range (IQR)] ratio of self-monitoring adherence for blood pressure, body weight, and body temperature at 100% (92-100%) and for oxygen saturation at 100% (91-100%). At 2 months, the intervention group's self-care behaviour score was significantly improved compared with the control group ( n = 11) [median (IQR): 16 (16-22) vs. 28 (20-36), P = 0.02], but the HF Knowledge Scale, the General Self-Efficacy Scale, and the Short Form-8 Health Survey scores did not differ between the groups., Conclusion: The novel mobile app for HF is feasible., Competing Interests: Conflicts of interest: T.Y. has received a consulting fee from Ambi Inc. M.O. and M.Y. are employees of Hitachi, Ltd. I.Y. has received speaker fees from Chugai Pharmaceutical Co., AstraZeneca, and Nippon Shinyaku Co. H.T. has received personal fees from MSD, Astellas, Pfizer, Bristol–Myers Squibb, Otsuka Pharmaceutical, Daiichi Sankyo, Mitsubishi Tanabe Pharma, Nippon Boehringer Ingelheim, Takeda Pharmaceutical, Bayer Yakuhin, Novartis Pharma, Kowa Pharmaceutical, Teijin Pharma, Medical Review Co., and the Japanese Journal of Clinical Medicine; non-financial support from Actelion Pharmaceuticals, Japan Tobacco Inc., Mitsubishi Tanabe Pharma, Nippon Boehringer Ingelheim, Daiichi Sankyo, IQVIA Services Japan, and Omron Healthcare Co.; and grants from Astellas, Novartis Pharma, Daiichi Sankyo, Takeda Pharmaceutical, Mitsubishi Tanabe Pharma, Teijin Pharma, and MSD outside the submitted work. The other authors declare no conflicts of interest relevant to the study. Hitachi, Ltd., had no role in the data collection, analysis, or interpretation of the data., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Data on the dose-dependent association of blood pressure (BP) and fasting plasma glucose (FPG) level with the risk of aortic dissection (AD) and aortic aneurysm (AA) are limited., Methods and Results: This observational cohort study included 3 358 293 individuals registered in a health checkup and claims database in Japan [median age, 43 (36-51) years; 57.2% men]. Individuals using BP- or glucose-lowering medications or those with a history of cardiovascular disease were excluded. In a mean follow-up period of 1 199 ± 950 days, 1 095 and 2 177 cases of AD and AA, respectively, were recorded. Compared with normal/elevated BP, hazard ratios (HRs) of Stage 1 and Stage 2 hypertension were 1.89 [95% confidence interval (CI): 1.60-2.22] and 5.87 (95% CI: 5.03-6.84) for AD and 1.37 (95% CI: 1.23-1.52) and 2.17 (95% CI: 1.95-2.42) for AA, respectively. Compared with normal FPG level, HRs of prediabetes and diabetes were 0.82 (95% CI: 0.71-0.94) and 0.48 (95% CI: 0.33-0.71) for AD and 0.94 (95% CI: 0.85-1.03) and 0.61 (95% CI: 0.47-0.79) for AA, respectively. The cubic spline demonstrated that the risk of AD and AA increased with increasing BP but decreased with increasing FPG level. Contour plots using generalized additive models showed that higher systolic BP and lower FPG level were associated with an elevated risk of AD and AA., Conclusions: Our analysis showed a dose-dependent increase in the risk of AD or AA associated with BP and a similar decrease associated with FPG, and also suggested a potential interaction between hypertension and hyperglycaemia in the development of AD and AA., Competing Interests: Conflict of interest: Research funding and scholarship funds (Hidehiro Kaneko and Katsuhito Fujiu) from Medtronic Japan; Biotronik Japan; SIMPLEX QUANTUM; Boston Scientific Japan; and Fukuda Denshi, Central Tokyo. Akira Okada is a member of the Department of Prevention of Diabetes and Lifestyle-related Diseases, which is a co-operative programme between The University of Tokyo and Asahi Mutual Life Insurance Company. The remaining authors have nothing to disclose. The funding sources had nothing with regard to the current study., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Coronavirus disease 2019 (COVID-19) has rapidly evolved to become a global pandemic, largely owing to the transmission of its causative virus through asymptomatic carriers. Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic people is an urgent priority for the prevention and containment of disease outbreaks in communities. However, few data are available in asymptomatic persons regarding the accuracy of polymerase chain reaction testing. In addition, although self-collected saliva samples have significant logistical advantages in mass screening, their utility as an alternative specimen in asymptomatic persons is yet to be determined., Methods: We conducted a mass screening study to compare the utility of nucleic acid amplification, such as reverse-transcription polymerase chain reaction testing, using nasopharyngeal swab (NPS) and saliva samples from each individual in 2 cohorts of asymptomatic persons: the contact-tracing cohort and the airport quarantine cohort., Results: In this mass screening study including 1924 individuals, the sensitivities of nucleic acid amplification testing with NPS and saliva specimens were 86% (90% credible interval, 77%-93%) and 92% (83%-97%), respectively, with specificities >99.9%. The true concordance probability between the NPS and saliva tests was estimated at 0.998 (90% credible interval, .996-.999) given the recent airport prevalence of 0.3%. In individuals testing positive, viral load was highly correlated between NPS and saliva specimens., Conclusion: Both NPS and saliva specimens had high sensitivity and specificity. Self-collected saliva specimens are valuable for detecting SARS-CoV-2 in mass screening of asymptomatic persons., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

In spot scanning proton therapy (SSPT), the spot position relative to the target may fluctuate through tumor motion even when gating the radiation by utilizing a fiducial marker. We have established a procedure that evaluates the delivered dose distribution by utilizing log data on tumor motion and spot information. The purpose of this study is to show the reliability of the dose distributions for liver tumors treated with real-time-image gated SSPT (RGPT). In the evaluation procedure, the delivered spot information and the marker position are synchronized on the basis of log data on the timing of the spot irradiation and fluoroscopic X-ray irradiation. Then a treatment planning system reconstructs the delivered dose distribution. Dose distributions accumulated for all fractions were reconstructed for eight liver cases. The log data were acquired in all 168 fractions for all eight cases. The evaluation was performed for the values of maximum dose, minimum dose, D99, and D5-D95 for the clinical target volumes (CTVs) and mean liver dose (MLD) scaled by the prescribed dose. These dosimetric parameters were statistically compared between the planned dose distribution and the reconstructed dose distribution. The mean difference of the maximum dose was 1.3% (95% confidence interval [CI]: 0.6%-2.1%). Regarding the minimum dose, the mean difference was 0.1% (95% CI: -0.5%-0.7%). The mean differences of D99, D5-D95 and MLD were below 1%. The reliability of dose distributions for liver tumors treated with RGPT-SSPT was shown by the evaluation of the accumulated dose distributions., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objectives: To identify predictive factors for remission by tocilizumab monotherapy in rheumatoid arthritis (RA) patients. Methods: This is a post hoc analysis of the SURPRISE study, a 2-year randomized, controlled study comparing the efficacy of tocilizumab with (ADD-ON) and without methotrexate (SWITCH). The primary endpoint was DAS28-ESR remission (<2.6) at week 24. The change in modified total Sharp score from baseline to week 52 (ΔmTSS/year) was also assessed as an endpoint. The effect of clinical parameters at baseline on remission was estimated by logistic regression analysis. Results: In SWITCH ( n  = 96), CRP, SAA, RF, and DAS28 at baseline showed predictive value for DAS28 remission in unadjusted analysis. Adjusted analysis confirmed SAA and DAS28 as predictive factors, with SAA having the highest value (ROC-AUC = 0.731). Furthermore, structural remission (ΔmTSS/year ≤ 0.5) rate was significantly higher in patients with SAA of < 50.0 μg/mL than other patients. In contrast, in ADD-ON ( n  = 98), only DAS28 showed predictive value for DAS28 remission. In patients with SAA < 50.0 μg/mL, both DAS28 remission and structural remission rate were comparable between SWITCH and ADD-ON. Conclusion: RA patients with low SAA levels at baseline may benefit similarly from tocilizumab with and without methotrexate. Trial registration number: NCT01120366.

Objectives: To identify the factors associated with the risk of diffuse alveolar hemorrhage (DAH) in patients with microscopic polyangiitis (MPA), focusing on other preexisting lung involvements such as interstitial lung disease (ILD) and airway disease. Methods: In this retrospective cohort study, we analyzed consecutive patients with myeloperoxidase-antineutrophil cytoplasmic antibody-positive MPA who had undergone chest computed tomography (CT) before starting treatment between 2006 and 2016. Patients who already had DAH at initial CT imaging were excluded. CT images were evaluated for the presence of ILD and airway disease. The association between preexisting lung involvements and the development of DAH was assessed using logistic regression models adjusted for various clinical characteristics. Results: We identified 113 patients (median age 72 years; median follow-up duration 39 months), and 27 (24%) of them developed DAH during the follow-up. Airway disease was identified in 41 (36%) patients and was independently associated with the development of DAH (adjusted odds ratio 6.86, 95% confidence interval 1.85-25.4). However, ILD identified in 45 (40%) patients was not associated with DAH. Conclusion: Our findings suggest that DAH in MPA occurs frequently in patients with airway disease. Attention to preexisting airway disease may help predict the development of DAH.

Objective: To assess risk factors for cytomegalovirus (CMV) disease with CMV re-activation in patients with rheumatic disease. Methods: The clinical data of consecutive patients with rheumatic disease who experienced CMV re-activation were examined. We evaluated the difference in various baseline factors at the first detection of CMV pp65 antigenemia on the development of CMV disease using logistic regression models. The changes of laboratory data in the 4 weeks before CMV re-activation were also assessed. Results: We identified 80 patients (median age [interquartile range] = 65.0 years [51.5-74.0]) with CMV re-activation. Oral candidiasis, serum albumin ≤30 g/L, and CMV pp65-positive cell count >5.6/10 5 polymorphonuclear leukocyte cells were found to be associated with CMV disease (odds ratio [OR] [95% CI] = 9.99 [2.02-49.50], 11.4 [1.94-67.40] and 6.80 [1.63-28.30], respectively). Moreover, decreases in serum albumin level and blood lymphocyte count in the 4 weeks before CMV re-activation also predicted CMV disease (OR [95% CI] = 2.02 [1.07-3.8] and 1.96 [1.09-3.54], respectively). Conclusion: In CMV re-activation patients with rheumatic disease, the presence of oral candidiasis, high CMV pp65 positive cell count, and hypoalbuminemia are possible risk factors for CMV disease.

Objectives: This study aimed to evaluate whether cardiac magnetic resonance imaging (MRI)-derived right ventricular (RV) assessment can facilitate risk stratification among patients with ischaemic cardiomyopathy who underwent surgical ventricular reconstruction (SVR)., Methods: We retrospectively analysed 53 patients who underwent SVR. The patients were preoperatively evaluated using cardiac MRI. Cine-MRI was acquired for left ventricular (LV) and RV volume. Gadolinium-enhanced MRI was performed to evaluate LV scarring. The mid-term (median, 58 months) risk factors of all-cause mortality and major adverse cardiac events were analysed., Results: A significant reduction in LV end-diastolic and end-systolic volume index and an increase in LV ejection fraction were observed early after SVR. RV end-diastolic volume index (RVEDVI) and RV end-systolic volume index (RVESVI) decreased after SVR (preoperative versus postoperative: RVEDVI, 71 ± 24 vs 62 ± 17 ml/m2, P = 0.006; RVESVI, 44 ± 26 vs 37 ± 16 ml/m2, P = 0.033), but RV ejection fraction did not change (preoperative versus postoperative: RV ejection fraction 40.8±14.6 vs 42.0±11.0%, P = 0.067). At follow-up, 25 deaths and 31 major adverse cardiac events occurred. After adjustment for age, creatinine level and preoperative mitral regurgitation grade, the Cox-hazard model indicated that RVEDVI [P = 0.006, hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01-1.05] and RVESVI [P = 0.007, HR 1.02, 95% CI 1.01-1.04] were significant predictors for all-cause mortality. As for major adverse cardiac events, RVEDVI (P = 0.007, HR 1.03, 95% CI 1.01-1.05), RVESVI (P = 0.002, HR 1.03, 95% CI 1.01-1.04) and RV ejection fraction (P = 0.018, HR 0.97, 95% CI 0.94-0.99) were significant., Conclusions: RV parameters were more sensitive than LV parameters for predicting worse outcomes following SVR. Preoperative assessment of RV volume and function using cardiac MRI may improve the risk stratification of SVR.

To investigate the relationship between ghrelin and both fetal and neonatal growth parameters and energy balance, we measured plasma ghrelin concentrations in 54 cord blood samples (male, n = 34; female, n = 20; gestational age, 37.0-41.6 wk; birth weight, 2206-4326 g) and 47 neonatal blood samples (male, n = 27; female, n = 20; postnatal d 3-8). The plasma ghrelin concentrations in cord blood ranged from 110.6-446.1 pmol/liter (median, 206.7 pmol/liter), which were equal to or higher than those in normal weight adults. These values were inversely correlated with birth weight (r = -0.40; P = 0.002), birth length (r = -0.36; P = 0.007), placental weight (r = -0.35; P = 0.01), and IGF-I concentration (r = -0.49; P = 0.0002), but were not significantly correlated with the GH concentration (r = 0.22; P = 0.12). The ghrelin concentrations in small for gestational age newborn were significantly higher than those in appropriate for gestational age newborns (P = 0.0008). The ghrelin concentrations in the vein were significantly higher than those in the artery in 8 cord blood samples (P = 0.01), which suggests that the placenta is an important source of fetal ghrelin. In neonates, the ghrelin concentrations ranged from 133.0-481.7 pmol/liter (median, 268.3 pmol/liter), which were significantly higher than those in cord blood (P < 0.0001). These results suggest that ghrelin may contribute to fetal and neonatal growth.

The expression and localization of long-form leptin receptor (OB-Rb) were studied immunocytochemically in the brain of fetal and adult rats using a polyclonal antibody that specifically recognized OB-Rb. At 14 days of gestation, immunoreactive cells were observed in the ventricular layer, which contains premature neuronal cells. At 18 days of gestation, they were weakly stained but obvious in the paraventricular nucleus (PVN), and ependymal cells also showed immunoreactivity. At birth, the immunoreactivity of OB-Rb in the PVN seemed to be much lower than that in adult rats and remained low during the suckling period. Considering the presence of neuroendocrine and structural neuronal abnormalities in Lepob/Lepob mice with genetic leptin deficiency, these results suggest that the expression of OB-Rb in premature neuronal cells may have some function, and that the regulation of energy balance by leptin through hypothalamic regions, such as PVN, may not yet be developed in the perinatal period.

To investigate the effect of leptin on fetal growth, serum leptin concentrations in venous cord blood were measured in 82 newborns (male = 43, female = 39, gestational age 36-42 weeks, birth weight 2,306-4,128 g). Serum leptin concentrations in cord blood ranged from 2.0 to 84.5 ng/mL (mean 19.9 +/- 17.4 ng/mL). Serum leptin concentrations in males (mean 15.3 +/- 15.6 ng/mL, range 2.0 to 79.3 ng/mL) were significantly (P = 0.011) lower than those in females (mean 25.0 +/- 18.0 ng/mL, range 2.1 to 84.5 ng/mL). Serum leptin concentrations in cord blood were positively correlated with birth weight (r = 0.555, P <0.0001), birth weight SD (r = 0.540, P <0.0001), Kaup index (r = 0.505, P <0.0001) and body weight/body height (r = 0.560, P <0.0001). The serum concentrations of estradiol and testosterone did not differ between males and females and did not correlate with the leptin concentration. It is unlikely that the gender difference in fetal leptin levels is due either to body fat content or distribution or to reproductive hormone status, but may be attributed to genetic differences between males and females.

A method for assay of 25-hydroxyvitamin D-24-hydroxylase (24-hydroxylase) activity in phytohemagglutinin (PHA)-stimulated lymphocytes was applied to determine whether vitamin D-dependent rickets type II (VDDR II) is hereditary. In normal lymphocytes incubated with PHA for 3 days, maximal and half-maximal responses of 24-hydroxylase were observed after exposure to 10(-8) mol/L and (1.3 +/- 0.4) x 10(-9) mol/L 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], respectively. These responses were similar to those of cultured skin fibroblasts. In contrast, after exposure to 10(-8), 10(-7), and 10(-6) mol/L 1,25-(OH)2D3, no 24-hydroxylase activity was detected in cells from patients with VDDR II, and intermediate activity was observed in cells from their parents. These findings indicated the presence of an intracellular receptor-effector system for 1,25-(OH)2D3 in peripheral lymphocytes. Heterozygotes of VDDR II could be identified, and autosomal recessive inheritance of the disease was demonstrated. Detection of heterozygotes of this disease was not possible by assay of inhibition of thymidine incorporation, another marker of the function of 1,25-(OH)2D3 in PHA-stimulated lymphocytes. Therefore, assay of 24-hydroxylase induction reflected the receptor status more closely than assay of inhibition of DNA biosynthesis. The assay of 24-hydroxylase activity in PHA-stimulated lymphocytes described here will be useful for diagnosis of VDDR II and study of families of patients with this disease.