Impact of the clinical frailty scale on long-term outcomes after transcatheter aortic valve implantation.

BACKGROUND: The semiquantitative Clinical Frailty Scale (CFS) is reportedly a useful marker for predicting short- and mid-term mortality after transcatheter aortic valve implantation (TAVI). We assessed the long-term prognostic impact of CFS in patients with severe aortic stenosis undergoing TAVI. METHODS: We prospectively assessed patients undergoing TAVI in Kokura Memorial Hospital using a 9-level CFS and enrolled 1594 patients after excluding patients with CFS 8-9. The patients were divided into the low (CFS level, 1-3; N = 842), intermediate (4; N = 469), and high (5-7; N = 283) groups according to their CFS levels. RESULTS: In the low, intermediate, and high groups, 3-year all-cause mortality rates were 17.4%, 29.4%, and 41.7% (P < .001) and composite rates of cardiovascular mortality and heart failure hospitalization were 12.1%, 19.1%, and 23.9% (P < .001), respectively. Multivariable analysis showed that higher frailty was independently associated with all-cause mortality (intermediate group: adjusted hazard ratio [HR], 1.63, 95% confidence interval [CI], 1.24-2.15, P < .001; high group: adjusted HR, 2.18, 95% CI, 1.59-2.99, P < .001) and composite of cardiovascular mortality and heart failure hospitalization (intermediate group: adjusted HR, 1.47, 95% CI, 1.04-2.08, P = .030; high group: adjusted HR, 1.66, 95% CI, 1.09-2.51, P = .018) and this result was consistent, irrespective of stratification based on age, sex, body mass index, left ventricular ejection fraction, Society of Thoracic Surgeons score, and New York Heart Association functional class without significant interaction. CONCLUSIONS: The simple CFS tool predicts the long-term adverse outcomes post-TAVI.

Zero-Contrast Left Atrial Appendage Closure in Patients With Chronic Kidney Disease.

BACKGROUND: Left atrial appendage closure (LAAC) usually requires contrast medium during the procedure. However, patients with chronic kidney disease (CKD) are at high risk of developing contrast nephropathy. This study aimed to assess the safety and feasibility of zero-contrast LAAC in patients with CKD.Methods and Results: Zero-contrast LAAC was attempted in 15 patients with CKD Stages 3b-5 who were not on hemodialysis. All procedures were performed successfully, without any periprocedural complications. At the 45-day follow-up, no device-related complications or acute kidney disease were observed. CONCLUSIONS: The strategy of zero-contrast LAAC in patients with CKD can be an acceptable option.

Mid-term impact of underfilling and overfilling of the SAPIEN 3 balloon-expandable transcatheter aortic valve implantation on mortality and valve function.

At present, underfilling or overfilling the volume of the balloon-expandable transcatheter heart valve (THV) is generally utilized in transcatheter aortic valve implantation (TAVI). However, no research has assessed the clinical impact of filling volume variations of the current-generation SAPIEN 3 THV. We analyzed the clinical data of 331 patients who underwent TAVI with SAPIEN 3 at our institution. Post-procedural echocardiographic and multidetector computed tomography (MDCT) scan data and 3-year prognoses according to each filling volume were assessed. The procedural outcomes and 3-year mortality rates were comparable among the underfilling, nominal filling, and overfilling groups. For all THV sizes, the THV area evaluated on post-procedural MDCT scan increased stepwise along with an elevated filling volume, thereby covering a wide range of native annulus area. Compared with patients in the nominal filling and overfilling groups, those with 23-mm THVs in the underfilling group had a smaller effective orifice area (EOA) (1.38 [IQR: 1.18-1.56] vs. 1.57 [IQR: 1.41-1.84] vs. 1.58 [IQR: 1.45-1.71] cm2, P = 0.02) and a higher mean transvalvular gradient (13.6 [IQR: 11.0-15.7] vs. 12.1 [IQR: 9.0-14.9] vs. 12.0 [IQR: 8.1-14.8] cm2, P = 0.04). In conclusion, by adjusting the filling volume of SAPIEN 3 using THV with limited sizes, continuously distributed native annulus areas were covered. The underfilling implantation technique had a minimal negative effect on the valve function of 23-mm THVs only. In the entire cohort, the filling volume variations did not affect the mid-term prognosis negatively.

Retusone A, a Guaiane-Type Sesquiterpene Dimer from Wikstroemia retusa and Its Inhibitory Effects on Histone Acetyltransferase HBO1 Expression.

Retusone A (1), a new sesquiterpene dimer consisting of two guaiane-type sesquiterpenoids, and oleodaphnal (2) were isolated from heartwood of Wikstroemia retusa (Thymelaeaceae). The planar structure of 1 was elucidated on the basis of HRESIMS and NMR spectroscopic data, and the relative stereochemistry was established by X-ray diffraction analysis. The absolute configuration of 1 was determined by electronic circular dichroism. Compound 1 suppressed luciferase reporter gene expression driven by the HBO1 (histone acetyltransferase binding to ORC1) gene promoter in human breast cancer MCF7 cells. Compound 1 also decreased the expression of endogenous HBO1 mRNA and protein, and inhibited proliferation of the cells. These results suggest that retusone A (1), which has a unique dimeric sesquiterpenoid structure with inhibitory activity against HBO1 expression, may contribute to the development of a novel therapeutic candidate for the treatment of breast cancer.

Continuous formation of small clusters with LGR5-positive cells contributes to tumor growth in a colorectal cancer xenograft model.

New cancer characteristics can be discovered by focusing on the process of tumor formation. Cancer stem cells (CSCs) are a key subpopulation, as they are theorized to be at the apex of the tumor hierarchy. We can better understand their function in the tumor hierarchy by using sectioned samples to observe the growth of tumors from their origins as CSCs. In this study, we evaluated the growth of moderate differentiated colorectal cancer from LGR5-positive cells, which is a CSC marker of colorectal cancer, using xenograft and three-dimensional culture models spatiotemporally. These cells express LGR5 at high levels and show CSC phenotypes. To detect them, we used a previously generated antibody that specifically targets LGR5, and were therefore able to observe LGR5-positive cells aggregating into small clusters (sCLs) over the course of tumor growth. Because these LGR5-expressing sCLs formed continuously during growth mainly in the invasive front, we concluded that the structure must contribute significantly to the expansion of CSCs and to tumor growth overall. We confirmed the formation of sCLs from gland structures using a three-dimensional culture model. In addition, sCLs exhibited upregulated genes related to stress response and partial/hybrid epithelial-mesenchymal transition (EMT), as well as genes reported to be prognosis factors. Finally, sCLs with high LGR5 expression were identified in clinical samples. Based on these results, we elucidate how sCLs are an important contributors to tumor growth and the expansion of CSCs.

Development of a Computer Application Used by Visiting Nurses, Physicians, and Patients/Caregivers to Prevent Indwelling Urinary Catheter Occlusion in the Community.

This study aimed to develop a computer application (software) for use by visiting nurses, physicians, and patients/caregivers, to support their care of long-term indwelling urinary catheters in the community. Development of this application involved: (1) confirmation of the intended purpose, users, and application construction; (2) establishment of the functional requirements for data sharing and communication among visiting nurses, physicians, and patients/caregivers; (3) design of three constituent "versions" of the application to be used by visiting nurses, physicians, and patients/caregivers, respectively; and (4) testing of the data sharing and communication functions. The application was designed to facilitate the prevention, assessment, and response to occlusion of indwelling urinary catheters during long-term use at home. This application is characterized by: (1) a unique design of three application "versions" that each reflect the specific care roles of its respective user group; (2) data sharing among the three groups according to their respective roles; and (3) the inclusion of caregivers as users. This article proposes a model that can inform the design of future applications for nursing professionals and patients and caregivers and provide a basis for future research on the development of healthcare applications supporting improvements in care.

A Polymer for Application as a Matrix Phase in a Concept of In Situ Curable Bioresorbable Bioactive Load-Bearing Continuous Fiber Reinforced Composite Fracture Fixation Plates.

The use of bioresorbable fracture fixation plates made of aliphatic polyesters have good potential due to good biocompatibility, reduced risk of stress-shielding, and eliminated need for plate removal. However, polyesters are ductile, and their handling properties are limited. We suggested an alternative, PLAMA (PolyLActide functionalized with diMethAcrylate), for the use as the matrix phase for the novel concept of the in situ curable bioresorbable load-bearing composite plate to reduce the limitations of conventional polyesters. The purpose was to obtain a preliminary understanding of the chemical and physical properties and the biological safety of PLAMA from the prospective of the novel concept. Modifications with different molecular masses (PLAMA-500 and PLAMA-1000) were synthesized. The efficiency of curing was assessed by the degree of convergence (DC). The mechanical properties were obtained by tensile test and thermomechanical analysis. The bioresorbability was investigated by immersion in simulated body fluid. The biocompatibility was studied in cell morphology and viability tests. PLAMA-500 showed better DC and mechanical properties, and slower bioresorbability than PLAMA-1000. Both did not prevent proliferation and normal morphological development of cells. We concluded that PLAMA-500 has potential for the use as the matrix material for bioresorbable load-bearing composite fracture fixation plates.

Gait characteristics of children with Williams syndrome with impaired visuospatial recognition: a three-dimensional gait analysis study.

Williams syndrome (WS) is a genetically based neurodevelopmental disorder characterized by intellectual disability and impaired visuospatial recognition. The aim of this study was to analyze the gait characteristics of WS children with impaired visuospatial recognition using a three-dimensional gait analysis (3DGA) to clarify the gait adaptation needed to compensate for it. 3DGA was performed in 8 WS children with impaired visuospatial recognition (mean age, 11.8 years) and 9 age-, sex-, height-, and weight-matched controls. Clinical data, fundamental motor tests, and gait variables while walking on a flat surface and walking up a mat were compared between the two groups, and the correlations between variables were analyzed in the WS children. WS children showed impairment of balance function without muscle weakness. In walking on a flat surface, the WS group showed reduced walking speed, short step length, increased variability of step length, increased knee flexion throughout the stance phase, increased horizontal pelvic range of motion (ROM), and a low Gait Deviation Index and a high Gait Profile Score, which are indices of gait quality. In walking up a mat, the WS group showed further reduced walking speed and decreased sagittal hip flexion and ankle dorsiflexion ROM in the swing phase. Impaired balance function was significantly correlated with increased variability of step length and decreased sagittal ankle dorsiflexion ROM in the swing phase. The detailed gait pattern of WS children with impaired visuospatial recognition was presented. These findings show that impaired visuospatial recognition and balance function contribute to gait adaptation.

Role of the Embodied Cognition Process in Perspective-Taking Ability During Childhood.

This study examined developmental changes in Level-2 visual perspective taking (VPT2) in 90 children aged 4-12 years and tested the role of their ability to mentally simulate changes to their bodily locations (self-motion imagery; SMI). Performance of a mental toy rotation task and a self-motion (SM) task (changing location of children) was superior to that of VPT2 and SMI tasks. Task performance of SMI was better than that of VPT2 before 10;0 (years;months). Furthermore, egocentric responses in VPT2 and SMI tasks were significantly more frequent than those in the mental rotation and SM tasks before 10;3. These findings suggest the involvement of embodied cognitive processes in perspective taking and the advantage of utilizing bodily information by age 10.

Osteoclasts secrete osteopontin into resorption lacunae during bone resorption.

Osteopontin (OPN) is a non-collagenous extracellular sialylated glycoprotein located in bone. It is believed to be one of the key components in osteoclast attachment to bone during resorption. In this study, we characterized OPN and other glycoproteins found in the resorption lacunae to confirm the role of osteoclasts in OPN secretion using electron microscopy and mass spectrometry. Additionally, we examined the glycan epitopes of resorption pits and the effects of different glycan epitopes on the differentiation and function of osteoclasts. Osteoarthritic femoral heads were examined by immunohistochemistry to reveal the presence of OPN in areas of increased bone metabolism in vivo. Our results demonstrate that human osteoclasts secrete OPN into resorption lacunae on native human bone and on carbonated hydroxyapatite devoid of natural OPN. OPN is associated with an elevated bone turnover in osteoarthritic bone under experimental conditions. Our data further confirm that osteoclasts secrete OPN into the resorption pit where it may function as a chemokine for subsequent bone formation. We show that α2,3- and α2,6-linked sialic acids have a role in the process of osteoclast differentiation. OPN is one of the proteins that has both of the above sialic residues, hence we propose that de-sialylation can effect osteoclast differentiation in bone.

Primary Use of the TruePath Crossing Device for Infrainguinal Chronic Total Occlusions With Intravascular Ultrasound Evaluation.

PURPOSE: To evaluate the use of the TruePath crossing device as the primary recanalization tool for infrainguinal chronic total occlusions (CTO). METHODS: A retrospective analysis was conducted of 50 patients (mean age 75 years; 26 men) with 55 infrainguinal CTOs treated with the TruePath between March 2017 and September 2017 at a single center. The mean occlusion length was 138±55 mm, and femoropopliteal lesions accounted for 65% of the 55 lesions. The primary outcome measure was CTO crossing using the TruePath alone; secondary outcomes were assisted success (>50% lumen gain using the TruePath), device-related complications, and intraluminal crossing evaluated by intravascular ultrasound (IVUS). RESULTS: Complete success was achieved in 33 (60%) of 55 lesions having a mean occlusion length of 145±72 mm. Among these, the true lumen crossing rate was 97% according to IVUS evaluation. Assisted success was achieved in 15 (68%) of the 22 failures. Complete/assisted success, in which the TruePath was thought to have contributed to CTO crossing, was attained in 48 (87%) of the 55 lesions. Three (5.5%) complications were observed: a perforation, an access-site hematoma, and acute occlusion; only the perforation was device related (1.8%). Multivariate analysis showed PACCS grade 4 (odds ratio 4.5, 95% confidence interval 1.33 to 15.5, p=0.02) was an independent predictor of TruePath failure. CONCLUSION: Primary use of the TruePath crossing device for infrainguinal CTOs demonstrated a satisfactory complete success rate and a high rate of IVUS-documented intraluminal crossing with few device-related complications. Severe calcification is an independent predictor of TruePath failure.

Plasma sE-cadherin and the plasma sE-cadherin/sVE-cadherin ratio are potential biomarkers for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation with endothelial dysfunction. Cadherins are adhesion molecules on epithelial (E-) and vascular endothelial (VE-) cells. Soluble (s) cadherin is released from the cell surface by the effects of proteases including matrix metalloproteinases (MMPs). OBJECTIVE: The aim of this study was to examine the associations of sE-/sVE-cadherin levels in plasma with the development of COPD. METHODS: Plasma sE-/VE-cadherin levels were measured by an enzyme-linked immunosorbent assay in 115 patients with COPD, 36 symptomatic smokers (SS), 63 healthy smokers (HS) and 78 healthy non-smokers (HN). sE-cadherin and MMP-7 levels in epithelial lining fluid (ELF) were measured in 24 patients (12 COPD and 12 control). RESULTS: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios were significantly higher in COPD and SS than in HS and HN groups, while plasma sVE-cadherin levels were lower in COPD than in HS and HN groups (p < 0.0001). sE-cadherin levels paralleled the severity of airflow limitation in both plasma (p < 0.01) and ELF (p < 0.05), while plasma sVE-cadherin levels were inversely correlated with the extent of emphysema (p < 0.05). MMP-7 levels were correlated with sE-cadherin levels in ELF. CONCLUSIONS: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios are potential biomarkers for COPD.

[Cognitive and linguistic abilities of a boy with PVL showing relatively higher VIQ compared to PIQ].

In this study, we investigated the cognitive processing and language abilities of a 13-year-old boy with moderate periventricular leukomalacia (PVL), spastic diplegia and exotropia who had discrepant scores in the verbal intelligence quotient (VIQ) and performance intelligence quotient (PIQ) in the Wechsler Intelligence Scale for Children, third edition (VIQ; 82 > PIQ; under 40). In the Kaufman Assessment Battery for Children and Das-Naglieri Cognitive Assessment System, his performance was poor at simultaneous processing compared to sequential processing. He could not copy three-dimensional figures, and he could place only two out of eight blocks correctly in the second level models of Benton three-dimensional block construction test, showing visuospatial impairment typical of patients with PVL. Despite the relatively high score in VIQ, there was a gap among the scores of the subtests in the Illinois Test of Psycholinguistic Abilities. He tended to get low scores in tests that required visual abilities. In addition, there was also an impairment in reading fluency tested by the Diagnostic Criteria and Medical Guideline for Specific Developmental Disorders. He was much less fluent in reading syllables, words or sentences (6.0 SD or more compared to 12-year-old boys). The relatively higher score in VIQ superficially suggests adequate language ability. However, in the present study, precise investigation revealed some discrepancies even within the field of language. Thus, defining stronger and weaker points of a patient is important in order to determine optimal medical or educational approaches.

Plasma cytokine profiles related to smoking-sensitivity and phenotypes of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) develops only in smoking-sensitive smokers and manifests heterogeneous phenotypes, including emphysema and non-emphysema types. We aimed to identify biomarkers related to the smoking-sensitivity and phenotypes of COPD. Among 240 smokers suggestive of COPD, we studied on four groups defined by % forced expiratory volume in one second (FEV1) and computed tomography-based pulmonary emphysema. Plasma concentrations of 33 inflammatory markers were measured in four groups as well as Non-smokers using multiplex protein arrays. IL-5, IL-7 and IL-13 were identified to be associated with smoking sensitivity and IL-6 and IL-10 were candidate biomarkers for airway-lesion dominant COPD.

Evaluation of layer-by-layer assembly systems for drug delivery and antimicrobial properties in orthopaedic application.

Layer-by-layer self-assembly systems were developed using monolayer and multilayer carriers to prevent infections and improve bone regeneration of porous Ti-6Al-4V scaffolds. These polymeric carriers incorporated (Gel/Alg-IGF-1 + Chi-Cef) and (4Gel/Alg-IGF-1 + Chi-Cef) on the surface of porous implants produced via electron beam melting (EBM). The results showed that the drug release from multilayer carriers was higher than that of monolayers after 14 days. However, the carrier containing Gel/Alg-IGF-1 + Chi-Cef exhibited more sustained behavior. Cell morphology was characterized, revealing that multilayer carriers had higher cell adhesion than monolayers. Additionally, cell differentiation was significantly greater for (Gel/Alg-IGF-1) + Chi-Cef, and (4Gel/Alg-IGF-1) + Chi-Cef multilayer carriers than for the monolayer groups after 7 days. Notably, the drug dosage was effective and did not interfere, and the cell viability assay showed safe results. Antibacterial evaluations demonstrated that both multilayer carriers had a greater effect on Staphylococcus aureus during treatment. The carriers containing lower alginate had notably less effect than the other studied carriers. This study aimed to test systems for controlling drug release, which will be applied to improve MG63 cell behavior and prevent bacterial accumulation during orthopaedic applications.

Use of the Phylobone database for the annotation of bone extracellular matrix proteins in reindeer (Rangifer tarandus).

Bone extracellular matrix (ECM) proteins play a key role in bone formation and regeneration, including structural and regulatory functions. The Phylobone database consists of 255 ECM protein groups from 39 species and can be used to support bone research. Here, we gathered bone ECM proteins from reindeer (Rangifer tarandus), a member of the Cervidae family. The importance of reindeer lies in their ability to regenerate their antlers, in both male and female individuals. Protein sequences were extracted from the National Center for Biotechnology Information's repository and selected by homology searches. We identified 215 proteins and their corresponding functional domains, which are putatively present in the bone ECM of reindeer. Protein sequence alignments have shown a high degree of conservation between R. tarandus and other members of the Cervidae family. This update expands the Phylobone database and shows that it is a useful resource for the preliminary annotation of bone ECM proteins in novel proteomes.

Surface modification of additive manufactured Ti6Al4V scaffolds with gelatin/alginate- IGF-1 carrier: An effective approach for healing bone defects.

The study investigates the potential of porous scaffolds with Gel/Alg-IGF-1 coatings as a viable candidate for orthopaedic implants. The scaffolds are composed of additively manufactured Ti6Al4V lattices, which were treated in an alkali solution to obtain the anatase and rutile phases. The treated surface exhibited hydrophilicity of <11.5°. A biopolymer carrier containing Insulin-like growth factor 1 was coated on the samples using immersion treatment. This study showed that the surface-modified porous Ti6Al4V scaffolds increased cell viability and proliferation, indicating potential for bone regeneration. The results demonstrate that surface modifications can enhance the osteoconduction and osteoinduction of Ti6Al4V implants, leading to improved bone regeneration and faster recovery. The porous Ti6Al4V scaffolds modified with surface coating of Gel/Alg-IGF-1 exhibited a noteworthy increase in cell viability (from 80.7 to 104.1%viability) and proliferation. These results suggest that the surface modified scaffolds have potential for use in treating bone defects.

Carcinoid Heart Disease With Hypoxemia.

Patent foramen ovale (PFO) complicated with carcinoid heart disease (CHD) can cause severe hypoxia and worsening clinical conditions. We report the case of a patient with CHD in poor general condition with multiple severe valve regurgitations and PFO, who underwent successful percutaneous closure of the PFO.

Application of a genetically engineered macrophage cell line for evaluating cellular effects of UV/US-treated poly(ethylene terephthalate) microplastics.

Microplastic (MP) pollution is a global environmental problem. To understand the biological effects of MPs on humans, it is essential to evaluate the response of human cells to model plastic particles that mimic environmental MPs in a sensitive and non-invasive manner. In this study, we investigated the preparation of poly(ethylene terephthalate) (PET) fragments with properties similar to those of environmental MPs by combining photo-oxidative degradation via ultraviolet (UV) irradiation with mechanical pulverization and hydrolysis via ultrasound (US) exposure. Combination of UV and US treatments decreased the particle size of PET fragments to 10.2 µm and increased their crystallinity and Young's modulus to 35.7 % and 0.73 GPa, respectively, while untreated PET fragments showed the particle size of 18.9 µm, the crystallinity of 33.7 %, and Young's modulus of 0.48 GPa. In addition, an increase in negative surface potential and O/C ratio were observed for UV/US-treated PET fragments, suggesting surface oxidation via UV/US treatment. Cytokine secretion from human macrophages was evaluated by a highly sensitive inflammation evaluation system using the HiBiT-based chemiluminescence detection method developed by genome editing technology. UV/US-treated PET fragments induced a 1.4 times higher level of inflammatory cytokine secretion on inflammatory macrophages than untreated ones, suggesting that the biological responses of PET fragments could be influenced by changes in material properties via oxidation. In conclusion, UV/US treatment enables efficient preparation of model plastic particles and is expected to provide new insights into the evaluation of biological effects using human cells. (240 words).