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Bilateral communication between bones and muscles is essential for healing composite bone-muscle injuries from orthopedic surgeries and trauma. However, these injuries are often characterized by exaggerated inflammation, which can disrupt bone-muscle crosstalk, thereby seriously delaying the healing of either tissue. Existing approaches are largely effective at healing single tissues. However, simultaneous healing of multiple tissues remains challenging, with little research conducted to date. Here we introduce collagen patches that overcome this overlooked issue by harnessing the plasticity of macrophage phenotypes. Phosphatidylserine liposomes (PSLs) capable of shifting the macrophage phenotype from inflammatory M1 into anti-inflammatory/prohealing M2 were coated on collagen patches via a layer-by-layer method. Original collagen patches failed to improve tissue healing under inflammatory conditions coordinated by M1 macrophages. In contrast, PSL-coated collagen patches succeeded in accelerating bone and muscle healing by inducing a microenvironment dominated by M2 macrophages. In cell experiments, differentiation of preosteoblasts and myoblasts was completely inhibited by secretions of M1 macrophages but unaffected by those of M2 macrophages. RNA-seq analysis revealed that type I interferon and interleukin-6 signaling pathways were commonly upregulated in preosteoblasts and myoblasts upon stimulation with M1 macrophage secretions, thereby compromising their differentiation. This study demonstrates the benefit of PSL-mediated M1-to-M2 macrophage polarization for simultaneous bone and muscle healing, offering a potential strategy toward simultaneous regeneration of multiple tissues. STATEMENT OF SIGNIFICANCE: Existing approaches for tissue regeneration, which primarily utilize growth factors, have been largely effective at healing single tissues. However, simultaneous healing of multiple tissues remains challenging and has been little studied. Here we demonstrate that collagen patches releasing phosphatidylserine liposomes (PSLs) promote M1-to-M2 macrophage polarization and are effective for simultaneous healing of bone and muscle. Transcriptome analysis using next-generation sequencing reveals that differentiation of preosteoblasts and myoblasts is inhibited by the secretions of M1 macrophages but promoted by those of M2 macrophages, highlighting the importance of timely regulation of M1-to-M2 polarization in tissue regeneration. These findings provide new insight to tissue healing of multiple tissues., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Riki Toita received a research grant from NGK Spark Plug Co., Ltd. (currently Niterra Co., Ltd.) Masahiro Kitamura, Atsushi Kato, Hideto Yamada, Shogo Yamaguchi, and Shinjiro Kasahara are employees of Niterra Co., Ltd. The remaining authors declare no competing interests., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Renin-angiotensin system inhibitors (RASI) reduce adverse cardiovascular events in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤40% and mild or moderate chronic kidney disease (CKD). However, RASI administration rate and its association with long-term outcomes in patients with CKD complicated by HF with LVEF >40% remain unclear., Methods: We analyzed 1923 consecutive patients with LVEF >40% registered within the multicenter database for hospitalized HF. We assessed RASI administration rate and its association with all-cause mortality among patients with mild or moderate CKD (estimated glomerular filtration rate [eGFR]: 30-60 mL/min/1.73 m 2 ). Exploratory subgroups included patients grouped by age (<80, ≥80 years), sex, previous HF hospitalization, B-type natriuretic peptide (higher, lower than median), eGFR (30-44, 45-59 mL/min/1.73 m 2 ), systolic blood pressure (<120, ≥120 mmHg), LVEF (41-49, ≥50%), and mineralocorticoid receptor antagonists (MRA) use., Results: Among patients with LVEF >40%, 980 (51.0%) had mild or moderate CKD (age: 81 [74-86] years; male, 52.6%; hypertension, 69.7%; diabetes, 25.9%), and 370 (37.8%) did not receive RASI. RASI use was associated with hypertension, absence of atrial fibrillation, and MRA use. After multivariable adjustments, RASI use was independently associated with lower all-cause mortality over a 2-year median follow-up (hazard ratio: 0.58, 95% confidence interval: 0.43-0.79, P = 0.001), and the mortality rate difference was predominantly due to cardiac death, consistent in all subgroups., Conclusions: Approximately one-third of HF patients with mild or moderate CKD and LVEF >40% were discharged without RASI administration and demonstrated relatively guarded outcomes., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Recently, patients with supra-normal left ventricular ejection fraction (snEF) are reported to have high risk of adverse outcomes, especially in women. We sought to evaluate sex-related differences in the association between LVEF and long-term outcomes in heart failure (HF) patients., Methods: The multicenter WET-HF Registry enrolled all patients hospitalized for acute decompensated HF (ADHF). We analyzed 3943 patients (age 77 years; 40.1% female) registered from 2006 to 2017. According to LVEF the patients were divided into the 3 groups: HF with reduced EF (HFrEF), mildly reduced EF (HFmrEF) and preserved EF. The primary endpoint was defined as the composite of cardiac death and ADHF rehospitalization after discharge., Results: In HFmrEF, implementation of guideline-directed medical therapy (GDMT) such as the combination of renin-angiotensin-system inhibitor (RASi) and β-blocker at discharge was significantly lower in women than men even after adjustment for covariates (p = 0.007). There were no such sex-related differences in HFrEF. Female sex was associated with higher incidence of the primary endpoint and ADHF rehospitalization after adjustment for covariates exclusively in HFmrEF. Restricted cubic spline analysis demonstrated a U-shaped relationship between LVEF and the hazard ratio of the primary endpoint showing higher event rate in HFmrEF and HFsnEF in women, but such relationship was not observed in men (p for interaction = 0.037)., Conclusions: In women, mrEF and snEF were associated with worse long-term outcomes. Additionally, sex-related differences in the GDMT implementation for HFmrEF highlight the need for further exploration, which might lead to creation of sex-specific guidelines to optimize HF management., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Hypertrophic cardiomyopathy (HCM) is a genetic disorder in which left ventricular outflow tract obstruction critically affects symptoms and prognosis. Traditionally, left ventricular outflow tract obstruction was primarily attributed to septal hypertrophy with systolic anterior motion of the mitral valve. However, recent evidence highlights significant contributions from the mitral valve and papillary muscle anomalies, as well as an apical-basal muscle bundle observed in HCM patients. Accurate morphological assessment is essential when considering septal reduction therapy. While transesophageal echocardiography and cardiac magnetic resonance are recommended for assessing the anomalous structures, four-dimensional computed tomography offers superior spatial resolution and multiplanar reconstruction capabilities. These features enable the evaluation of details of the morphological anomalies, such as the apical-basal muscle band, papillary muscle anomalies, subaortic stenosis, and right ventricular outflow tract obstruction. Based on the detailed assessment of these morphological features, four-dimensional computed tomography has been utilized for planning of surgical correction in a comprehensive HCM center. This approach facilitates the intervention strategies and may improve outcomes in septal reduction therapy for obstructive HCM., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Sequential vaccination with the 13-valent pneumococcal protein conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for patients undergoing hemodialysis; however, evidence for the efficacy of these pneumococcal vaccines for patients undergoing hemodialysis is limited to a single dose. We aimed to evaluate the prognosis of patients undergoing hemodialysis who received vaccination with PPSV23 alone versus sequential vaccination with PCV13 and PPSV23., Methods: Patients undergoing hemodialysis who were vaccinated with PPSV23 alone (PPSV23 group) or PCV13 followed by PPSV23 (PCV13+PPSV23 group) between 2014 and 2016 were included; the observation period was three years from the first injection. Patients who underwent hemodialysis between 2011 and 2012 were included as controls. After propensity score matching using age, sex, dialysis vintage, diabetes history, pneumonia history, and serum albumin and creatinine levels, survival analysis was performed., Results: The study included 89, 71, and 319 patients in the PPSV23, PCV13+PPSV23, and control groups, respectively. After propensity score matching, the PPSV23 and control group 1 (79 patients each) and the PCV13+PPSV23 and control group 2 (61 patients each) were compared. Significant differences were observed in the survival rate between the PPSV23 group and control group 1 (p = 0.005) but not between the PCV13+PPSV23 group and control group 2. Pneumonia-related mortality in the two vaccinated groups did not differ significantly during the observation period., Conclusions: Patients who received PPSV23 had a favorable prognosis; however, no positive effect was demonstrated in the PCV13+PPSV23 group., Competing Interests: Declaration of interest The authors declare no competing interests., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Interest in clinical course preceding heart failure (HF) exacerbation has grown, with a greater emphasis placed on patients' clinical factors including precipitant factor (PF). Large-scale studies with precise PF documentation and temporal-outcome variation remain limited., Methods: We reviewed prospectively collected 2412 consecutive patient-level records from a multicenter Japanese registry of hospitalized patients with HF (West Tokyo Heart Failure2 Registry: 2018-2020). Patients were categorized based on PFs: behavioral (i.e., poor adherence to physical activity, medicine, or diet regimen), treatment-required (i.e., anemia, arrhythmia, ischemia, infection, thyroid dysfunction or other conditions as suggested exacerbating factors), and no-PF. The composite outcomes of HF rehospitalization and death within 1 year after discharge and HF rehospitalization were individually assessed., Results: Median patient age was 78 years (interquartile range: 68-85 years), and 1468 (61%) patients had documented PFs, of which 356 (15%) were considered behavioral. The behavioral PF group were younger, more male and had past HF hospitalization history compared to those in the other groups (all p < 0.05). Although risk of in-hospital death was lower in the behavioral PF group, their risk of composite outcome was not significantly different from the treatment-required group (hazard ratio [HR] 1.19 [95% confidence interval {CI} 0.93-1.51]) and the no-PF group (HR 1.28 [95%CI 1.00-1.64]). Furthermore, the risk of HF rehospitalization was higher in the behavioral PF group than in the other two groups (HR 1.40 [95%CI 1.07-1.83] and HR 1.39 [95%CI 1.06-1.83], respectively)., Conclusion: Despite a better in-hospital prognosis, patients with behavioral PFs were at significantly higher risk of HF rehospitalization., Competing Interests: Declaration of Competing Interest Dr. Shiraishi received research grants from the SECOM Science and Technology Foundation and the Uehara Memorial Foundation, as well as honoraria from Otsuka Pharmaceutical Co. Ltd. and Ono Pharmaceutical Co. Ltd. Dr. Kohsaka received an unrestricted research grant from the Department of Cardiology at Keio University School of Medicine, Bayer Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Novartis Pharmaceutical Co. Ltd., and AstraZeneca Pharmaceutical Co. Ltd. The authors declare that they have no conflicts of interest. There are no patents, products in development, or marketed products to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Human norovirus (HuNoV) is a major cause of acute gastroenteritis and foodborne diseases worldwide with public health concern, yet no antiviral therapies have been developed. In this study, we aimed to screen crude drugs, which are components of Japanese traditional medicine, ''Kampo'' to see their effects on HuNoV infection using a reproducible HuNoV cultivation system, stem-cell derived human intestinal organoids/enteroids (HIOs). Among the 22 crude drugs tested, Ephedra herba significantly inhibited HuNoV infection in HIOs. A time-of-drug addition experiment suggested that this crude drug more preferentially targets post-entry step than entry step for the inhibition. To our knowledge, this is the first anti-HuNoV inhibitor screen targeting crude drugs, and Ephedra herba was identified as a novel inhibitor candidate that merits further study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Immobilized metal ion affinity chromatography (IMAC) is one of the most common purification techniques for histidine-tagged proteins (His-tagged proteins). IMAC enables the purification of His-tagged proteins at high purity on the basis of coordination bonds between His-tags and metal ions (such as Ni 2+ , Co 2+ , and Cu 2+ ) immobilized on the matrices in columns. However, IMAC requires low-pH solutions or high-concentration imidazole solutions for eluting His-tagged proteins, which can affect protein conformation and activity. The present study provides a His-tagged protein purification method using zirconia particles modified with phosphate groups. This method is based on the electrostatic attractions between a His-tag moiety of proteins and phosphate groups on the zirconia particles; this method requires only high-concentration salt solutions at pH 7.0 for eluting the proteins. A column packed with phosphate-modified zirconia particles was demonstrated to enable the purification of two model His-tagged proteins-His-tagged green fluorescent protein and His-tagged alkaline phosphatase fused with maltose binding protein. Thus, this chromatography method is useful for purifying His-tagged proteins without any pH stress or additives. Additionally, because of the mechanical properties of the zirconia particles, this technique enables high-performance purification at a high flow rate., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

High-performance and cost-effective purification is necessary for the development of antibody drugs. This study found that nanoparticles of zirconia modified with phosphate groups selectively adsorb immunoglobulin G (IgG) antibodies against serum proteins with high adsorption capacity. The IgG antibodies collected from the zirconia nanoparticle surfaces retain their molecular conformation. Importantly, zirconia nanoparticles have the highest affinity for human IgG antibodies among tested mammalian IgG antibodies. The affinity for human IgG subclasses is in the order IgG3 > IgG1 > IgG2, which contrasts with a conventional ligand (Protein A) that has a lower affinity for IgG3. Because zirconia nanoparticles are chemically and mechanically stable, they can be utilized for the purification of antibody drugs not only in batch methods but also in chromatography as a process upstream or downstream of Protein A chromatography and even as an alternative process., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Glomerulonephritis (GN) with crescents and IgA deposits in kidney biopsy poses a frequent diagnostic and therapeutic dilemma because of multiple possibilities., Methods: Native kidney biopsies showing glomerular IgA deposition and crescents (excluding lupus nephritis) were identified from our biopsy archives between 2010 and 2021. Detailed clinicopathologic features were assessed. One-year clinical follow-up on a subset of cases was obtained., Results: A total of 285 cases were identified, and these clustered into IgA nephropathy (IgAN, n  = 108), Staphylococcus or other infection-associated GN/infection-related GN (SAGN/IRGN, n  = 43), and antineutrophil cytoplasmic antibody-associated GN (ANCA-GN, n  = 26) based on a constellation of clinicopathologic features, but 101 cases (group X) could not be definitively differentiated. The reasons have been elucidated, most important being atypical combination of clinicopathologic features and lack of definitive evidence of active infection. Follow-up (on 72/101 cases) revealed that clinicians' working diagnosis was IgAN in 43%, SAGN/IRGN in 22%, ANCA-GN in 28%, and others in 7% of the cases, but treatment approach varied from supportive or antibiotics to immunosuppression in each subgroup. Comparing these cases as "received immunosuppression" versus "non-immunosuppression," only 2 features differed, namely C3-dominant staining, and possibility of recent infection (both higher in the no-immunosuppression group) ( P  < 0.05). Renal loss was higher in the non-immunosuppression subgroup, but not statistically significant ( P  = 0.11)., Conclusion: Diagnostic overlap may remain unresolved in a substantial number of kidney biopsies with glomerular crescents and IgA deposits. A case-by-case approach, appropriate antibiotics if infection is ongoing, and consideration for cautious immunosuppressive treatment for progressive renal dysfunction may be needed for best chance of renal recovery., (© 2022 Published by Elsevier Inc. on behalf of the International Society of Nephrology.)

By using EDTPA-modified zirconia particles that selectively adsorb immunoglobulins in a column, we developed a chromatography separation system for efficient concentrating and purifying of IgM from hybridoma culture supernatants. Hybridoma culture supernatants containing IgMs were diluted 3-fold with 10 mM phosphate buffer (pH 7.0) and passed through the column. During this process, zirconia particles selectively adsorbed these IgMs, and most of the contaminating proteins flowed out into the flow-through. The adsorbed IgMs were easily eluted with a small volume of 400 mM phosphate buffer (pH 8.0), and high-concentration IgM solutions were prepared. Subsequent simple processing using a Capto™ Core 400 cartridge column provided highly purified IgM. The operation is easy, and the activity of IgM is maintained because the purification process is performed using only neutral ranges of phosphate buffers. Here, we showed that anti-globoside and anti-CDw75 IgM purified by this method can be used to stain cervical cancer and Burkitt lymphoma cells that specifically express these respective tumor-associated carbohydrate antigens., Competing Interests: Declaration of competing interest The National Institute of Advanced Industrial Science and Technology holds patents (JP6172687B2, US9796785B2, and EP2993184B1) that relate to the materials reported in this article. The authors declare no other competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: When treating cancer patients, the progression of symptoms is accompanied by the deterioration of systemic conditions and motor function. From a risk-benefit perspective, a certain level of physical function must be maintained to continue cancer treatment. Recently, outpatient cancer treatment has become more common. Motor function is important to determine the feasibility of continuing cancer treatment. The study aimed to evaluate the motor function of patients with visceral cancer using locomo tests established by Japanese Orthopaedic Association., Methods: Locomo tests were performed, and the results were compared with data from non-cancer individuals. Background data were matched by propensity score matching. Data from 53 cancer patients (group C) were compared with that of 75 non-cancer patients (group N)., Results: The average score in the two-step test of group C was lower than that of group N (1.27: 1.37, p = 0.004). The average function in the stand-up test of group C was worse than that of group N (p = 0.001). The average score in the 25-question geriatric locomotive function scale (GLFS) of group C was significantly higher than that of group N (19.92: 5.29, SE 2.21, p < 0.001). Higher 25-question GLFS scores indicate reduced mobility. The proportion of the locomo stage 2 in group C was significantly higher than in group N (51%: 13%, p < 0.001). The results of the two field tests revealed a clinically minimal difference between the two groups, but a statistically significant difference. Locomo tests may be detect potential motor dysfunction in outpatient cancer patients with apparently maintained motor function., Conclusions: Even in cancer patients who attend outpatient clinics, their motor functions could be potentially impaired. Therapeutic interventions to maintain and enhance motor function for cancer patients could be useful for continuing cancer treatment, and furthermore, improving prognosis., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Objective: To clarify the impacts of health literacy on mortality, readmission, and quality of life (QOL) in the secondary or tertiary prevention of cardiovascular diseases (CVD) through a meta-analysis., Methods: Six electronic databases were searched on June 11, 2020. Observational studies involving patients with CVD, health literacy as an exposure factor and mortality, readmission, or QOL as outcomes were included in this study. Two researchers screened the retrieved articles and extracted data independently. The meta-analysis calculated the pooled relative risk of mortality and readmission. We also assessed the body of evidence based on Grading of Recommendations Assessment, Development and Evaluation (GRADE)., Results: Following screening of 1616 studies, 16 observational studies were included. The mean rate of low health literacy was 32.8%. All studies focusing on QOL showed significant impacts of health literacy. Pooled relative risk was 1.621 (95% confidence interval: 1.089-2.412) for mortality and 1.184 (95% confidence interval: 1.035-1.355) for readmission, indicating significant effects of health literacy. GRADE assessment showed "LOW" certainty for each outcome., Conclusion: Low health literacy was significantly associated with increased mortality and hospital readmission and decreased QOL in patients with CVD., Practice Implications: Considering low health literacy in clinical practice is very important to improve prognosis of CVD patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: The aim of this cohort study among community-dwelling older adults aged over 70 years was to investigate the influence of occlusal support on tooth loss, and to determine predictive factors for tooth loss for each occlusal support category using multilevel analyses., Methods: Participants were 812 older adults who completed the baseline survey and the follow-up survey 6 years later. The Eichner index was used to evaluate occlusal support status. A generalized estimating equation (GEE) logistic regression analysis was used to examine the influence of occlusal support status on tooth loss while adjusting for various factors at individual and tooth levels. Similar analyses were separately performed in each Eichner class to determine predictive factors for tooth loss., Results: The GEE showed that a decline in occlusal support increased the risk of tooth loss (Eichner A: reference category, Eichner B: odds ratio (OR) = 1.96, p < 0.001, Eichner C: OR = 3.04, p < 0.001). Stratified analysis showed that deeper periodontal pockets and abutment teeth for fixed partial dentures were significantly associated with tooth loss, regardless of occlusal support. In Eichner A, the presence of an opposing tooth was advantageous in protecting the tooth, and a missing adjacent tooth was not significantly associated with tooth loss. An opposing tooth was associated with the risk of tooth loss in Eichner B, and a missing adjacent tooth was significantly associated with tooth loss in Eichner B and C., Conclusions: A decline in occlusal support accelerated tooth loss. Predictive factors for tooth loss varied depending on occlusal support status., Clinical Significance: Occlusal support is an important factor in preventing tooth loss. Dentition conditions such as missing adjacent teeth and the presence of opposing teeth increase the risk of tooth loss in participants with poor occlusal support. Dental personnel need to carefully examine dentition conditions to assess the risk of occlusal collapse., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Vascular and bleeding complications are common after transcatheter aortic valve implantation (TAVI) and are associated with worse outcomes. The plug-based Manta (M) vascular closure device (VCD) is a novel option to achieve haemostasis for large-bore arterial access sites., Objective: We aimed to compare vascular and bleeding complications between the M-VCD and the established suture-based Perclose ProGlide (P)-VCD., Methods: From February to September 2019 a total of 578 patients underwent transfemoral TAVI at a single high-volume centre. Access site closure was performed using M-VCD in 195 patients (33.7%) and P-VCD in 383 patients (66.3%). We assessed vascular and access site-related complications as well as bleeding events according to the Valve Academic Research Consortium-2 definition., Results: Overall vascular complications occurred less frequently in the M-VCD group (10.7% vs. 19.0%, p = 0.011) driven by a significantly lower rate of major vascular events (2.0% vs. 6.5%, p = 0.025). Access site-related complications were significantly less frequent in the M-VCD cohort (10.7% vs. 16.6%, p = 0.048). The M-VCD was associated with significantly lower rates of major (0.5% vs. 4.4%, p = 0.009) and life-threatening bleeding (0% vs. 2.3%, p = 0.032). In multivariable analysis, the use of M-VCD was the only independent predictor of vascular complications (odds ratio 0.54, 95% confidence interval 0.32-0.91, p = 0.022)., Conclusions: The M-VCD was associated with a reduction of vascular and access-site complications as well as severe bleeding after transfemoral TAVI compared to the P-VCD in this observational study., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Although more children with congenital heart disease (CHD) are reaching adulthood, they generally have some impairment compared to their healthy peers. Few studies have investigated the effect of exercise training on health-related quality of life (HRQOL) and/or physical activity in children with CHD., Purpose: The purpose of this study was to systematically review the effect of exercise training on HRQOL and/or physical activity and the types of training used in general., Methods: We searched relevant articles published from 2000 to 2021 in English and included intervention studies for children with CHD younger than 20 years who underwent exercise training. Afterwards, we excluded the studies not using HRQOL or physical activity as outcome measures, classified the extracted information according to outcome measures and types of interventions, and assessed the risk of bias of the included studies., Results: Finally, 10 articles were selected, and HRQOL in 3 articles and physical activity in 3 articles showed improvement after exercise training. However, 4 articles did not show improvement in these outcome measures, and 9 of the articles had a high risk of bias in blinding. Sport-based or play-based interventions were used in 5 articles, and prescribed or structured ones were used in 5 articles., Conclusion: Although exercise training for children with CHD may improve their HRQOL and/or physical activity, more studies are needed to assess the effect statistically. In children with CHD, sport-based or play-based interventions could be used as well as prescribed or structured interventions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Objectives: The aim of this study was to examine the predictive value of preprocedural computed tomography (CT)-based risk stratification of coronary obstruction during transcatheter aortic valve replacement (TAVR) on the basis of geometric measurements on postprocedural CT., Background: Proper patient selection for additional procedures to prevent coronary obstruction during TAVR has not been adequately evaluated., Methods: Pre- and postprocedural computed tomographic scans of 28 patients treated using bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction (BASILICA) and TAVR were analyzed. Using the postprocedural computed tomographic images, threatened coronary obstruction (TCO) was defined as: 1) ostial obstruction (adherence of the transcatheter heart valve [THV] to the coronary ostium with leaflet extension above the ostium); and/or 2) sinus sequestration (THV adherence to the sinotubular junction [STJ] with leaflet extension above the STJ) and was substratified into complete and incomplete types., Results: A total of 51 leaflets were evaluated (88% surgical tissue valves) after excluding leaflets not visible on CT (n = 5). On postprocedural CT, complete TCO was observed in 25.4% (13 of 51 leaflets). On preprocedural CT, leaflets were at high risk for complete TCO (incidence 53%) if the virtual THV-to-coronary distance (VTC) was <3.0 mm, or if the virtual THV-to-STJ distance (VTSTJ) was <1.0 mm with STJ height - leaflet length <0 mm (leaflet-STJ mismatch). Leaflets were at low risk (incidence 0%) if the VTC was ≥3 mm and VTSTJ was ≥3.0 mm or STJ height - leaflet length was ≥+2.0 mm. Of 28 leaflets treated using BASILICA, complete TCO was seen in 35.7% (n = 10), due to sinus sequestration (100%) with coexisting ostial obstruction (30%). Actual coronary events occurred in 7.1% (n = 2) because of leaflet prolapse, corresponding to an absolute risk reduction by BASILICA of 29% (P = 0.021)., Conclusions: Risk assessment of coronary obstruction after TAVR may improve with a multiparametric approach incorporating VTC, VTSTJ, and leaflet-STJ mismatch. BASILICA appeared to reduce actual coronary events even in leaflets with anticipated coronary obstruction., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac rupture (CR) is a catastrophic complication of acute myocardial infarction. Primary percutaneous coronary intervention (pPCI) reduces the incidence of CR. This study aimed to investigate the clinical risk factors and characteristics of CR after pPCI., Methods: This was a retrospective, case-control, multicenter study. We enrolled 2444 consecutive patients with ST-elevation myocardial infarction (STEMI) who had undergone pPCI between 2009 and 2015; 33 patients experienced CR (1.35%): 19 were assigned as early CR (≤72 h) and 14 as late CR (>72 h). The 132 controls were randomly selected from the 2411 STEMI patients without CR, by matching institutions at a 1:4 ratio., Results: Multivariate logistic regression revealed that female sex, acute hyperglycemia, thrombocytopenia (platelets <15 × 10 4 /µL), and incomplete revascularization [post-PCI thrombolysis in myocardial infarction (TIMI) <3] were independent risk factors for CR (p<0.05). Older age, female sex, and emergency surgical repair were strongly associated with in-hospital death, which occurred in 66.7% of CR patients (p<0.05). Univariate logistic regression adjusted for age and sex revealed that low systolic blood pressure, anterior infarction, acute hyperglycemia, Killip class >1, and post-PCI TIMI <3 were significantly associated with early CR, and that Killip class >1 and thrombocytopenia were strongly associated with late CR. Early CR occurred more frequently between 12:00 and 21:00 h, whereas the peak incidence of late CR was bimodal between 6:00-12:00 and 21:00-24:00 h., Conclusions: In STEMI patients after pPCI, acute hyperglycemia and thrombocytopenia are new risk factors for early and late CR, respectively. Clinical risk factors and time of occurrence of early and late CR may differ in the PCI era., (Copyright © 2021. Published by Elsevier Ltd.)

Objectives: The aim of this study was to investigate changes in quality of life (QoL) after transcatheter tricuspid valve repair (TTVR) for tricuspid regurgitation (TR)., Background: TTVR provides feasible and durable efficacy in reducing TR, but its clinical benefits on QoL still remain unclear., Methods: In 115 subjects undergoing TTVR for severe functional TR, QoL was evaluated using the 36-Item Short Form Health Survey (SF-36) and the Minnesota Living With Heart Failure Questionnaire (MLHFQ). All-cause mortality, heart failure (HF) rehospitalization, and a composite endpoint of all-cause mortality, HF rehospitalization, and repeat TTVR were recorded as clinical events., Results: Successful device implantation was achieved in 110 patients (96%). Moderate or less TR at discharge was achieved in 95 patients (83%). Mean SF-36 physical component summary (PCS) score improved from 34 ± 9 to 37 ± 9 points (+3 points; 95% CI: 1-5 points; P = 0.001), mean SF-36 mental component summary score improved from 49 ± 9 to 51 ± 10 points (+2 points; 95% CI: 0-4 points; P = 0.017), and mean MLHFQ score decreased from 29 ± 14 to 20 ± 15 points (-8 points; 95% CI: -11 to -5 points; P < 0.001). Baseline PCS, moderate or less TR at discharge, and baseline massive or torrential TR were associated with 1-month change in PCS score (P < 0.05). Change in PCS score after 1 month predicted HF rehospitalization after TTVR (adjusted HR: 0.74 [95% CI: 0.60-0.92] per 5-point increase in PCS score; P = 0.008)., Conclusions: This study demonstrates that TTVR provides improvement in QoL in patients with relevant TR. TR reduction to a moderate or less grade was associated with improvement of SF-36 and MLHFQ scores. Further, global QoL was associated with clinical outcomes and might serve as a future outcome surrogate following TTVR., Competing Interests: Funding Support and Author Disclosures Dr Lurz has been a consultant to Abbott Structural Heart, Edwards Lifesciences, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to introduce a novel clinically relevant nomenclature system for the TV and determine the relative incidence of each morphological type., Background: With the rapid development of transcatheter tricuspid valve (TV) repair techniques, there is a growing recognition of the variability in leaflet morphology and a need for a unified nomenclature, which could aid in procedural planning and execution., Methods: Patients from 4 medical centers (2 in Europe, 2 in the United States) referred for transesophageal echocardiography (TEE) to assess native TV function, were retrospectively analyzed for leaflet morphology with the use of a novel classification scheme. Four morphological types were identified: type I, 3 leaflets; type II, 2 leaflets; type IIIA, 4 leaflets with 2 anterior; type IIIB, 4 leaflets with 2 posterior; type IIIC, 4 leaflets with 2 septal; and type IV, >4 leaflets., Results: A total of 579 patients were analyzed: mean age 78.1 ± 8.0 years, 50.4% female, 70.9% in atrial fibrillation, and 32.2% with previous left heart surgery or transcatheter intervention. Tricuspid regurgitation was moderate or less in 9.4%, severe in 40.5%, massive in 32.3%, and torrential in 17.7%. The etiology of tricuspid regurgitation was primary in 9.4%, mixed in 10.8%, and secondary in all of the other patients (18.6% atriogenic/isolated). The incidence of type I morphology was 312 of 579 (53.9%), type II was 26 of 579 (4.5%), type IIIA was 15 of 579 (2.6%), type IIIB was 186 of 579 (32.1%), type IIIC was 22 of 579 (3.8%), and type IV was 14 of 579 (2.4%)., Conclusions: A novel TV leaflet nomenclature classification scheme can be used to identify 4 types of TV morphologies with the use of TEE imaging. From this multinational retrospective study, the TV has 3 well defined leaflets in only ∼54% of patients and 4 functional leaflets in ∼39% of patients, with type IIIB (2 posterior leaflets) being the most common of the latter. The utility of this classification scheme deserves further study., Competing Interests: Funding Support and Author Disclosures Dr. Hahn received speaker fees from Edwards Lifesciences; consulting for Abbott Vascular, Boston Scientific, and Medtronic; equity with Navigate; and is the Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored trials, for which she receives no direct industry compensation. Dr. Bae is a consultant for Abbott Vascular. Dr. Hausleiter has received research support and speaker honoraria from and serves as a consultant for Abbott Vascular and Edwards Lifesciences. Dr. Nabauer has received speaker fees from Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

We report a case of prolonged motivational deficit as a sequela of high altitude cerebral edema (HACE), the most severe form of neuropsychiatric dysfunction arising from traveling to high altitude. Magnetic resonance imaging of the brain showed hyperintense lesions in the globi pallidi bilaterally on T2-weighted images. Single-photon emission computed tomography showed hypoperfusion in dorsolateral and orbital prefrontal cortices bilaterally and in the anterior cingulate cortex. This case suggests that a prolonged motivational deficit can occur in patients with HACE. The case may also suggest that HACE can cause network disturbances between the prefrontal cortex and the globi pallidi., (Copyright © 2020 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to examine the relationship between the difficulty of activity using the arms and mild cognitive impairment (MCI), the relationship between the difficulty of activity using the arms and manual function, and cognitive function in patients with coronary artery disease (CAD)., Methods: We conducted a cross-sectional study of 263 non-dementia patients who met the study criteria from 2328 CAD patients. MCI was estimated with the Japanese version of the Montreal Cognitive Assessment (MoCA-J). The difficulty of activity using the arms was evaluated using the Disability of the Arm, Shoulder, Disability of the Arm, Shoulder and Hand and Hand (DASH) questionnaire. Manual function was evaluated by pinch strength and handgrip strength., Results: Age (odds ratio, 1.10), three-fingered pinch strength (odds ratio, 0.69), and DASH score (odds ratio, 1.03) were independently associated with MCI in the multivariable logistic regression analysis. Hemoglobin (β=-0.15), handgrip strength (β=-0.37), and MoCA-J score (β=-0.15) were independently associated with DASH score (Model 1: p<0.001, adjusted R 2 =0.33); hemoglobin (β=-0.17), eGFR (β=-0.14), three-fingered pinch strength (β=-0.25), and MoCA-J score (β=-0.14) were independently associated with DASH score in the multivariate regression analysis (Model 2: p<0.001, adjusted R 2 =0.31)., Conclusions: The difficulty of activity using the arms was independently associated with manual and cognitive function and MCI in CAD patients., (Copyright © 2020. Published by Elsevier Ltd.)

Background: The relationship between mild cognitive impairment (MCI) and pinch strength in patients with cardiovascular disease is unclear. The purpose of the present study was to examine the associations among MCI and pinch strength and to determine a pinch strength cut-off value for use in the assessment of MCI., Methods: We conducted a cross-sectional study of 135 patients with cardiovascular disease but without probable dementia. MCI was estimated with the Japanese version of the Montreal Cognitive Assessment. We classified patients into the normal cognitive group and MCI group and compared their clinical characteristics, handgrip strength, and pinch strength. The relation between MCI and pinch strength was clarified with logistic regression analysis, and the cut-off value for three-fingered pinch strength was determined by receiver operating characteristic curve analysis., Results: The incidence of MCI was 37.0 %. Significant differences between the two groups were identified for age, body mass index, hemoglobin, estimated glomerular filtration rate, albumin, dyslipidemia, use of nitrates, educational background, handgrip strength, and pinch strength. After multivariate analysis, three-fingered pinch strength was significantly associated with MCI (odds ratio 0.77, p= 0.02). The cut-off value of three-fingered pinch strength for predicting MCI was 6.75 kgf (area under the curve = 0.71; p< 0.001)., Conclusions: Pinch strength was one independent factor significantly associated with MCI in patients with cardiovascular disease. The determination of a cut-off value for three-fingered pinch strength that can predict MCI may be one important factor in the early screening for MCI in the daily clinical setting., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Endobronchial volatile sulfur compounds in patients with lung abscess or lung cancer were measured using the Oral Chroma™ gas chromatograph. High levels of hydrogen sulfide and methyl mercaptan were observed in some patients with lung abscess but not in patients with lung cancer. Measuring endobronchial volatile sulfur compounds could be useful for the rapid diagnosis of lung abscess caused by obligate anaerobes., Competing Interests: Declarations of interest None., (Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Many candidates with ischaemic functional mitral regurgitation (FMR) have previously undergone coronary artery bypass grafting (CABG), in which transcatheter mitral valve repair can be reasonable for ameliorating the deteriorated hemodynamic and heart failure symptoms. We sought to elucidate the outcomes of MitraClip (MC) implantation in patients with symptomatic ischaemic FMR after CABG., Methods: We investigated clinical characteristics, outcomes and predictive impact of previous CABG on mortality in ischaemic FMR patients who underwent MC implantation from two high-volume centres in Germany., Results: We enrolled 159 patients who previously underwent CABG. Compared with a reference group that did not previously undergo CABG (n = 182), the cohort consisted of more elderly patients (75.0, standard deviation [SD] 7.7 versus 72.9, SD 9.6 years, p = 0.028), more men (84% vs. 69%, p < 0.001), and reduced tricuspid annular plane systolic excursion (14.0, SD 4.0, vs. 16.6, SD 4.6 mm, p < 0.0001). The CABG group showed similar outcomes regarding procedural success (91% vs. 94%, p = 0.24) and 30-day mortality (5.0% vs. 6.0%, p = 0.68), but worse survival after MC implantation (log-rank p = 0.019, hazard ratio 1.56 [95% confidence interval (CI) 1.08-2.26]). After propensity score matching (n = 224), the hazard ratio was 1.18 [95%CI 0.76-1.84] without statistical significance (p = 0.46)., Conclusions: Transcatheter mitral valve repair using the MC is a viable treatment option for patients with symptomatic ischaemic FMR after CABG. Although the baseline characteristics seemed to point to sick patients, CABG itself had only a modest impact on survival., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to evaluate the predictors of left ventricular outflow tract (LVOT) obstruction after transcatheter mitral valve replacement (TMVR)., Background: LVOT obstruction is a major concern with TMVR, but limited data exist regarding its predictors and impact on outcomes., Methods: Patients with pre-procedural multidetector row computed tomography (MDCT) undergoing TMVR for failed mitral bioprosthetic valves (valve-in-valve), annuloplasty rings (valve-in-ring), and mitral annular calcification (valve-in-MAC) were included in this study. Echocardiographic and procedural characteristics were recorded, and comprehensive assessment with MDCT was performed to identify the predictors of LVOT obstruction (defined as an increment of mean LVOT gradient ≥10 mm Hg from baseline). The new LVOT (neo-LVOT) area left after TMVR was estimated by embedding a virtual valve into the mitral annulus on MDCT, simulating the procedure., Results: Among 194 patients with pre-procedural MDCT undergoing TMVR (valve-in-valve, 107 patients; valve-in-ring, 50 patients; valve-in-MAC, 37 patients), LVOT obstruction was observed in 26 patients (13.4%), with a higher rate after valve-in-MAC than valve-in-ring and valve-in-valve (54.1% vs. 8.0% vs. 1.9%; p < 0.001). Patients with LVOT obstruction had significantly higher procedural mortality compared with those without LVOT obstruction (34.6% vs. 2.4%; p < 0.001). Receiver-operating characteristic curve analysis showed that an estimated neo-LVOT area ≤1.7 cm 2 predicted LVOT obstruction with sensitivity of 96.2% and specificity of 92.3%., Conclusions: LVOT obstruction after TMVR was associated with higher procedural mortality. A small estimated neo-LVOT area was significantly associated with LVOT obstruction after TMVR and may help identify patients at high risk for LVOT obstruction., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to determine the prognostic factors for acute encephalopathy with reduced diffusion (AED) during the acute phase through retrospective case evaluation., Methods: The participants included 23 patients with AED. The diagnosis of AED was based on their clinical course and radiological findings. We divided the patients into severe and non-severe groups based on the neurodevelopmental outcome. The severe group included seven patients (median age, 21 months; range, 6-87 months) and the non-severe group included 16 patients (19 months, 9-58 months). Clinical symptoms, laboratory data and electroencephalogram (EEG) findings within 48 h from the initial seizure onset were compared between the two groups to identify neurological outcome predictors., Results: The incidence of coma 12-24 h after onset, serum creatinine (Cr) levels within 2 h after onset, maximum aspartate aminotransferase (AST) levels within 24 h after onset, and the rate of electrographic seizures in EEG were significantly higher in the severe group (Coma, 80%; Cr, 0.40 mg/dl, 0.37-0.73; AST, 363 IU/L, 104-662; electrographic seizures, 80%) than the non-severe group (Coma, 0%; Cr, 0.29 mg/dL, 0.19-0.45; AST, 58.5 IU/L, 30-386; electrographic seizures, 0%)., Conclusions: Coma 12-24 h after onset, elevation of Cr levels within 2 h after onset, elevation of AST levels within 24 h after onset, and non-convulsive status epileptics (NCSE) in comatose patients were early predictors of severe AED. Patients in a coma after a febrile seizure should be checked for NCSE signs in EEG to terminate NCSE without delay., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Phosphatidylinositol phosphate (PIP) synthetase is a promising target for the development of new anti-mycobacterium compounds. We previously reported that myo-inositol 1-methylenephosphonate showed inhibitory activity against PIP synthetase. Herein, we report the synthesis of unprotected myo-inositol 4-methylenephosphonate, a constitutional isomer of myo-inositol 1-methylenephosphonate and found that the stereoselective hydrogenation of vinylphosphonate proceeded via Rh catalysis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)