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Background: Asthma in the elderly needs more attention in an aging society. However, it is likely to remain underdiagnosed and undertreated. This study aimed to clarify clinical characteristics of new-onset asthma in the elderly, describing the prevalence, predictive factors, and comorbidities after asthma diagnosis of new-onset asthma in the elderly in the general population. Methods: This community-based prospective cohort study enrolled 9804 generally healthy participants (30–74 years old) in Nagahama City, and conducted a follow-up assessment after 5 years. Elderly participants were those aged ≥65 years at baseline. Patients with new-onset asthma were defined as participants without asthma at baseline assessment and with asthma at the follow-up assessment. Results: Among the 7948 participants analyzed in this study, 28 (1.4%) elderly and 130 (2.2%) non-elderly had new-onset asthma. Multiple logistic regression analysis revealed low forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and high blood eosinophil counts at baseline as predicting factors for new-onset asthma in the elderly. Additionally, subsequent incidence of new-onset asthma was higher in elderly participants with both predictors (high blood eosinophil counts and low FEV1/FVC at baseline) than those with none or one of the predictors before asthma diagnosis. Lastly, elderly patients with new-onset asthma had more frequent comorbidity of moderate to severe sleep disordered breathing than those non-elderly. Conclusions: Eosinophilic inflammation and airflow obstruction may predict subsequent new-onset asthma after the age of 65 years. Revealing the characteristics of new-onset asthma in the elderly can aid in the prevention of underdiagnosed asthma.

Background: Obesity and increased body mass index (BMI) are the known risk factors for adult-onset asthma. Serum free fatty acid (FFA) and other blood lipid levels are generally elevated in patients with obesity and may be involved in the onset of asthma. However, it remains largely unknown. This study aimed to elucidate the relationship between plasma fatty acids and new-onset asthma. Methods: This community-based Nagahama Study in Japan enrolled 9804 residents. We conducted self-reporting questionnaires, lung function tests, and blood tests at baseline and 5 years later as follow-up. At the follow-up, plasma fatty acids were measured using gas chromatography-mass spectrometry. Body composition analysis was also measured at the follow-up. The associations between fatty acids and new-onset asthma were evaluated using a multifaceted approach, including targeted partial least squares discriminant analysis (PLS-DA). Results: In PLS-DA for new-onset asthma, palmitoleic acid was identified as the fatty acid most associated with asthma onset. In the multivariable analysis, higher levels of FFA, palmitoleic acid, or oleic acid were significantly associated with new-onset asthma, independent of other confounding factors. The high body fat percentage itself was not the relevant factor, but showed a positive interaction with plasma palmitoleic acid for new-onset asthma. When stratified by gender, the impacts of higher levels of FFA or palmitoleic acid on new-onset asthma remained significant in females, but not in males. Conclusions: Elevated levels of plasma fatty acids, particularly palmitoleic acid, may be a relevant factor for new-onset asthma.

Abstract Little is known about the association of prolonged cough, a common and troublesome symptom, with metabolic pathways. We aimed to clarify this association using data from the Nagahama cohort, a prospective study of participants from the general population. Self-report questionnaires on prolonged cough were collected at baseline and 5-year follow-up assessments. Blood tests at follow-up were used for gas chromatography-mass spectrometry-based metabolomics. The association between metabolites and prolonged cough was examined using the partial least squares discriminant analysis and multiple regression analysis. Among the 7432 participants, 632 had newly developed prolonged cough at follow-up, which was defined as “new-onset prolonged cough”. Low plasma citric acid was significantly associated with new-onset prolonged cough, even after the adjustment of confounding factors including the presence of asthma, upper airway cough syndrome (UACS), and gastroesophageal reflux disease (GERD). A similar association was observed for isocitric acid, 3-hydroxybutyric acid, and 3-hydroxyisobutyric acid. The analysis of these four metabolites revealed that citric acid had the strongest association with new-onset prolonged cough. This significant association remained even when the analysis was confined to participants with UACS or GERD at baseline or follow-up, and these associations were also observed in participants (n = 976) who had prolonged cough at follow-up regardless of baseline status. In conclusion, low blood citric acid may be associated with prolonged cough.

Bronchial thermoplasty (BT) is effective in some severe asthma patients; however, the specific asthma phenotypes that produce a good response to BT are not fully understood. Clinical data were retrospectively reviewed in severe asthma patients who underwent BT at a single institution in Japan. At the follow-up assessment, the Asthma Quality of Life Questionnaire (AQLQ) scores (P = 0.003), maintenance oral corticosteroid doses (P = 0.027), and exacerbation frequency (P = 0.017) were significantly improved, while prebronchodilator-forced expiratory volume in 1 second (% predicted) did not significantly change (P = 0.19). When we grouped the patients into 2 groups according to their body mass index levels, the AQLQ scores were more improved in patients with overweight/obesity than those with normal weight (P = 0.01). This study showed that patients with non-controlled severe asthma exhibiting overweight/obesity and low quality of life had potential benefits from BT.

Abstract Blood eosinophil count is a useful measure in asthma or COPD management. Recent epidemiological studies revealed that body mass index (BMI) is positively associated with eosinophil counts. However, few studies focused on the role of adiposity and fatty acid-related metabolites on eosinophil counts, including the effect of genetic polymorphism. In this community-based study involving 8265 participants (30–74 year old) from Nagahama city, we investigated the relationship between eosinophil counts and serum levels of fatty acid-related metabolites. The role of MDC1, a gene that is related to eosinophil counts in our previous study and encodes a protein that is thought to be involved in the repair of deoxyribonucleic acid damage, was also examined taking into account its interaction with adiposity. Serum levels of linoleic acid (LA) and β-hydroxybutyric acid (BHB) were negatively associated with eosinophil counts after adjustment with various confounders; however, there were positive interactions between serum LA and BMI and between serum BHB and BMI/body fat percentages in terms of eosinophil counts. In never-smokers, there was positive interaction for eosinophil counts between the CC genotype of MDC1 rs4713354 and BMI/body fat percentages. In conclusion, both serum LA and BHB have negative impacts on eosinophil counts, while adiposity shows robust positive effects on eosinophil counts, partly via genetic background in never-smokers.

Immune checkpoint inhibitors (ICIs) have been used to treat lung cancer. Several types of ICI-related interstitial lung diseases have been reported, including organizing pneumonia, non-specific interstitial pneumonia, and diffuse alveolar damage. However, pembrolizumab-associated bronchiolitis requiring treatment for persistent cough has not yet been reported. Here, we describe a patient who developed dry cough while being treated with pembrolizumab for lung adenocarcinoma. Radiography and lung biopsy findings indicated bronchiolitis. His cough improved after the discontinuation of pembrolizumab and treatment with erythromycin, an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting β2 agonist. Keywords: Bronchiolitis, Immune checkpoint inhibitors-related lung disease, Inhaled corticosteroid, Long-acting β2 agonist, Long-acting muscarinic antagonist, Lung cancer

ObjectivesThis study aimed to evaluate the efficacy of preoperative computed tomography in assessing mitral annulus anatomy and the posterior annular plication rate in mitral valve repair with annuloplasty.MethodsFrom July 2018 to August 2023, we performed robotic mitral valve repair with ring annuloplasty using a semi-rigid ring in 100 patients. Preoperative anatomical assessment of the mitral annulus was conducted by three-dimensional computed tomography. The ring size was selected based on the perioperative commissure-to-commissure length or the anterior leaflet area.ResultsThe mean commissure-to-commissure length, posterior mitral annular length, and minimum distance between the left circumflex artery and mitral annulus values were 31, 109, and 3.8 mm, respectively. No postoperative left circumflex artery injury or ring detachment was recorded. The mean plication rate (length of the posterior side of the prosthetic ring/posterior annular length) was 0.68, and it did not differ among each prosthetic ring size. The posterior plication rate (duplicate ring size 19.4) was a factor influencing the postoperative transmitral mean pressure gradient of 5 mmHg or higher. Freedom from moderate or severe mitral regurgitation was not different between the two groups above and below the posterior plication rate × ring size of 19.4 (p = 0.73), with an event-free rate of 97% vs. 96% in 3 years, respectively.ConclusionsPreoperative evaluation of the mitral annular anatomy is useful for safe mitral valve repair with ring annuloplasty. Determining ring size by focusing on the posterior annular plication rate may be a new method for ring size selection.

Abstract Background Aortic valve perforation is a rare complication of blunt chest trauma. We report a case of delayed aortic insufficiency presenting several months after trauma. Case presentation A 17-year-old male presented to the emergency department with traumatic brain injuries and blunt chest trauma, but no evidence of cardiac injuries. Three months later, he developed acute heart failure due to severe aortic valve regurgitation with left ventricular dysfunction. A sizable tear in the right coronary cusp caused aortic insufficiency. He was treated successfully by surgical replacement with an aortic bioprosthesis. Conclusion We reported a successful surgical case of valve replacement for delayed aortic valve perforation. Delayed valve perforation should be kept in mind after blunt chest trauma.

Abstract Background Recently, improvements in the repair of tetralogy of Fallot have increased the need for reoperation in adulthood, and it’s not rare that these reoperation candidates suffer from biventricular failure. However, there are no firm treatment guidelines, and each country, and even each facility, treats each case individually. Case presentation We report the successful staged treatment of pulmonary regurgitation and pacemaker-induced cardiomyopathy with biventricular failure in adulthood in a case of complete atrioventricular block after tetralogy of Fallot repair in childhood. We planned a staged therapeutic strategy with preoperative left ventricular volume reduction with medication, following surgical pulmonary valve replacement concomitant epicardial lead implantation on the lateral basal wall, placed just beneath the generator pocket through 3rd intercostal space. in addition to postoperative intervention with a defibrillator to adjust cardiac resynchronization therapy, resulted in improvement of symptoms. Conclusion In a patient with biventricular failure after TOF repair, a staged treatment strategy involving medication, PVR, and CRT with a combination of epicardial and intravenous leads could be a useful treatment worth trying before heart transplantation.

Abstract Background The median arcuate ligament syndrome (MALS) is a disease in which the celiac artery is compressed by the arcuate ligament and causes stenosis. If abdominal pain or an aneurysm is observed in the head of the pancreas, it is necessary to release the arcuate ligament, and recently laparoscopic surgery has been reported. However, the indication for treatment in asymptomatic cases is unknown. The treatment for asymptomatic MALS in patients with gastric cancer who are indicated for surgery is also novel. Case presentation A 70-year-old female was found with early gastric cancer in the middle body of the stomach. An enhanced CT scan showed no metastasis, but a gallstone and stenosis of the celiac artery due to the MALS were found. The patient underwent releasing median arcuate ligament after lymph node dissection. A median arcuate ligament was located on the ventral side of the left gastric artery stump, and the celiac artery was exposed when cutting it off. The operation time was 4 h and 59 min, and the bleeding was 6 ml. It took about 5 min to dissect the medial arcuate ligament. The postoperative course was satisfactory, and the patient was discharged 7 days after the operation. CT scan and 3-D CT angiography were performed about 2 months after the operation, and the findings revealed that the celiac artery's stenosis resolved. Conclusion The patient underwent laparoscopic gastrectomy and simultaneously the median arcuate ligament release under an excellent visual field. Therefore, median arcuate ligament release may be considered if MALS is found in a gastrectomy case.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

BackgroundThere is no existing reliable and practical method for predicting the prognosis of acute respiratory distress syndrome (ARDS).ObjectiveWe aimed to clarify the association between the ROX index, which is calculated as the ratio of peripheral oxygen saturation divided by the fraction of inspired oxygen to the respiratory rate, and the prognosis of patients with ARDS under ventilator support.MethodsIn this single-center retrospective cohort study from prospectively collected database, eligible patients were categorized into three groups based on ROX tertiles. The primary outcome was the 28-day survival, and the secondary outcome was 28-day liberation from ventilator support. We performed multivariable analysis using the Cox proportional hazards model.ResultsAmong 93 eligible patients, 24 (26%) patients died. The patients were divided into three groups according to the ROX index (< 7.4, 7.4-11, ≥ 11), with 13, 7, and 4 patients dying in the groups, respectively. A higher ROX index was associated with lower mortality; adjusted hazard ratios [95% CIs] for increasing tertiles of ROX index: 1[reference], 0.54[0.21-1.41], 0.23[0.074-0.72] (P = 0.011 for trend) and a higher rate of successful 28-day liberation from ventilator support; adjusted hazard ratios [95% CIs] for increasing tertiles of ROX index: 1[reference], 1.41[0.68-2.94], 2.80[1.42-5.52] (P = 0.001 for trend).ConclusionsThe ROX index at 24 h after initiating ventilator support is a predictor of outcomes in patients with ARDS and might inform initiation of more advanced treatments.

Abstract Objective We investigated the effect of morphological diversity of the tricuspid valve with multiple posterior leaflets on the technical outcomes of tricuspid valve repair. Methods From April 2016 to November 2020, 141 patients were diagnosed with secondary tricuspid regurgitation associated with left heart disease and underwent tricuspid valve repair. We retrospectively analyzed the clinical and echocardiographic data of patients who underwent both preoperative and postoperative transthoracic echocardiography. We divided the patients into two groups according to the surgical technique used to treat tricuspid regurgitation: ring annuloplasty alone (Group 1, n = 109) or additional approximation of leaflet edges (edge-to-edge repair) with ring annuloplasty (Group 2, n = 32). We measured the morphological diversity of the tricuspid valve during the operation in all patients. Results The preoperative tricuspid regurgitation score was higher in Group 2 than in Group 1 (2.1 ± 0.78 vs. 1.6 ± 0.7, respectively; p = 0.0046), and Group 2 contained more patients with two posterior leaflets than Group 1 [20 (63%) vs. 36 (33%), respectively; p = 0.003]. The univariate and multivariate logistic regression analyses showed that the presence of two posterior leaflets was an independent risk factor for additional procedures during tricuspid valve repair (odds ratio, 2.6; 95% confidence interval, 1.1–6.1; p = 0.033). Conclusions Additional procedures to reduce tricuspid regurgitation were required more frequently in patients with two posterior leaflets of the tricuspid valve. The morphological diversity of two posterior leaflets is a potential risk factor for a more complicated tricuspid repair.

Abstract There have been no report of objective clinical characteristics or prognostic factors that predict fatal outcome of acute respiratory distress syndrome (ARDS) since the Berlin definition was published. The aim of this study is to identify clinically available predictors that distinguish between two phenotypes of fatal ARDS due to pneumonia. In total, 104 cases of Japanese patients with pneumonia-induced ARDS were extracted from our prospectively collected database. Fatal cases were divided into early (

Mouse trophoblast stem cells (TSCs) have been established and maintained using hyperglycemic conditions (11 mM glucose) for no apparent good reason. Because glucose metabolites are used as resources for cellular energy production, biosynthesis, and epigenetic modifications, differences in extracellular glucose levels may widely affect cellular function. Since the hyperglycemic culture conditions used for TSC culture have not been fully validated, the effect of extracellular glucose levels on the properties of TSCs remains unclear. To address this issue, we investigated the gene expression of stemness-related transcription factors in TSCs cultured in the undifferentiated state under various glucose concentrations. We also examined the expression of trophoblast subtype markers during differentiation, after returning the glucose concentration to the conventional culture concentration (11 mM). As a result, it appeared that the extracellular glucose conditions in the stem state not only affected the gene expression of stemness-related transcription factors before differentiation but also affected the expression of marker genes after differentiation, with some line-to-line variation. In the TS4 cell line, which showed the largest glucose concentration-dependent fluctuations in gene expression among all the lines examined, low glucose (1 mM glucose, LG) augmented H3K27me3 levels. An Ezh2 inhibitor prevented these LG-induced changes in gene expression, suggesting the possible involvement of H3K27me3 in the changes in gene expression seen in LG. These results collectively indicate that the response of the TSCs to the change in the extracellular glucose concentration is cell line-dependent and a part of which may be epigenetically memorized.

New robotic system that uses three dimensional measurement with solid object recognition—3D-MOS (Three Dimensional Move on Sensing)—based on visual servoing technology was designed and the on-board hand-eye-dual-cameras robot system has been developed to reduce risks of radiation exposure during decontamination processes by filter press machine that solidifies and reduces the volume of irradiation contaminated soil. The feature of 3D-MoS includes; (1)the both hand-eye-dual-cameras take the images of target object near the intersection of both lenses' centerlines, (2) the observation at intersection enables both cameras can see target object almost at the center of both images, (3) then it brings benefits as reducing the effect of lens aberration and improving the detection accuracy of three dimensional position. In this study, accuracy validation test of interdigitation of the robot's hand into filter cloth rod of the filter press—the task is crucial for the robot to remove the contaminated cloth from the filter press machine automatically and for preventing workers from exposing to radiation—, was performed. Then the following results were derived; (1) the 3D-MoS controlled robot could recognize the rod at arbitrary position within designated space, and all of insertion test were carried out successfully and, (2) test results also demonstrated that the proposed control guarantees that interdigitation clearance between the rod and robot hand can be kept within 1.875[mm] with standard deviation being 0.6[mm] or less.

Direct laser-writing techniques have attracted attention for their use in two- and three-dimensional printing technologies. In this article, we report on a micropatterning process that uses femtosecond laser reductive sintering of mixed CuO/NiO nanoparticles. The writing speed, laser fluence, and incident total energy were varied to investigate the influence of heat accumulation on the micropatterns formed by these materials. Heat accumulation and the thermal history of the laser irradiation process significantly affected the material composition and the thermoelectric properties of the fabricated micropatterns. Short laser irradiation durations and high laser fluences decrease the amount of metal oxide in the micropatterns. Selective fabrication of p-type and n-type thermoelectric micropatterns was demonstrated to be possible with control of the reduction and reoxidization reactions through the control of writing speed and total irradiation energy.

The enhancement of aggregation-induced emission (AIE) is presented on the basis of the strategy for improving solid-state luminescence by employing multiple o-carborane substituents. We synthesized the modified triphenylamines with various numbers of o-carborane units and compared their optical properties. From the optical measurements, the emission bands from the twisted intramolecular charge transfer (TICT) state were obtained from the modified triphenylamines. It was notable that emission efficiencies of the multi-substituted triphenylamines including two or three o-carborane units were enhanced 6- to 8-fold compared to those of the mono-substituted triphenylamine. According to mechanistic studies, it was proposed that the single o-carborane substitution can load the AIE property via the TICT mechanism. It was revealed that the additional o-carborane units contribute to improving solid-state emission by suppressing aggregation-caused quenching (ACQ). Subsequently, intense AIEs were obtained. This paper presents a new role of the o-carborane substituent in the enhancement of AIEs.