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.

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.

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.

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.

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.

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).

Assessing Potential Risks of Future Redo Transcatheter Aortic Valve Replacement in Asian Patients.

Background: In the Asian cohort, data are limited on the risk for coronary obstruction due to sinus of Valsalva (SOV) sequestration in redo transcatheter aortic valve replacement (TAVR) procedures. Objectives: The aim of this study was to assess the potential risk for coronary obstruction in simulated redo TAVR in Asian patients. Methods: Post-TAVR computed tomographic data from 788 patients who received balloon-expandable (BE) SAPIEN 3 transcatheter aortic valves (TAVs) and 334 patients who received self-expanding (SE) Evolut R or Evolut PRO TAVs were analyzed. The risk for coronary obstruction due to SOV sequestration in redo TAVR, defined as the TAV commissure level above the sinotubular junction (STJ) and a TAV-to-STJ distance <2.0 mm in each coronary sinus, was retrospectively evaluated. Results: The potential risks for coronary obstruction due to SOV sequestration at 1 or both coronary arteries were identified in 52.1% of the BE TAV group and 71.3% of the SE TAV group (P < 0.001). After adjusting for multiple covariates, STJ diameter, STJ height, TAV oversizing degree by area, and implantation depth were independently associated with SOV sequestration risk in the BE TAV group, whereas STJ diameter and implantation depth were independently associated with SOV sequestration risk in the SE TAV group. Conclusions: Coronary obstruction due to SOV sequestration in redo TAVR may occur in a substantial number of Asian patients. This finding suggests the importance of considering the structural feasibility of future redo TAVR when implanting the first TAV, especially in Asian patients with long life expectancy.

Impact of Transjugular Intracardiac Echocardiography-Guided Self-Expandable Transcatheter Aortic Valve Implantation on Reduction of Conduction Disturbances.

BACKGROUND: A high permanent pacemaker implantation (PPI) risk remains a concern of self-expandable transcatheter aortic valve implantation, despite the continued improvements in implantation methodology. We aimed to assess the impact of real-time direct visualization of the membranous septum using transjugular intracardiac echocardiography (ICE) during transcatheter aortic valve implantation on reducing the rates of conduction disturbances including the need for PPI. METHODS: Consecutive patients treated with Evolut R and Evolut PRO/PRO+ from February 2017 to September 2022 were included in this study. We compared outcomes between the conventional implantation method using the 3-cusps view (3 cusps without ICE group), the recent method using cusp-overlap view (cusp overlap without ICE group), and our novel method using ICE (cusp overlap with ICE group). RESULTS: Of the 446 patients eligible for analysis, 211 (47.3%) were categorized as the 3 cusps without ICE group, 129 (28.9%) were in the cusp overlap without ICE group, and 106 (23.8%) comprised the cusp overlap with ICE group. Compared with the 3 cusps without ICE group, the cusp overlap without ICE group had a smaller implantation depth (2.2 [interquartile range, 1.0-3.5] mm versus 4.3 [interquartile range, 3.3-5.4] mm; P<0.001) and lower 30-day PPI rates (7.0% versus 14.2%; P=0.035). Compared with the cusp overlap without ICE group, the cusp overlap with ICE group had lower 30-day PPI rates (0.9%; P=0.014), albeit with comparable implantation depths (1.9 [interquartile range, 0.9-2.9] mm; P=0.150). Multivariable analysis showed that our novel method using ICE with the cusp-overlap view was independently associated with a 30-day PPI rate reduction. There were no group differences in 30-day all-cause mortality (1.4% versus 1.6% versus 0%; P=0.608). CONCLUSIONS: Our novel implantation method using transjugular ICE, which enable real-time direct visualization of the membranous septum, achieved a predictably high position of prostheses, resulting in a substantial reduction of conduction disturbances requiring PPI after transcatheter aortic valve implantation.

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.

Phylobone: a comprehensive database of bone extracellular matrix proteins in human and model organisms.

The bone extracellular matrix (ECM) contains minerals deposited on highly crosslinked collagen fibrils and hundreds of non-collagenous proteins. Some of these proteins are key to the regulation of bone formation and regeneration via signaling pathways, and play important regulatory and structural roles. However, the complete list of bone extracellular matrix proteins, their roles, and the extent of individual and cross-species variations have not been fully captured in both humans and model organisms. Here, we introduce the most comprehensive resource of bone extracellular matrix (ECM) proteins that can be used in research fields such as bone regeneration, osteoporosis, and mechanobiology. The Phylobone database (available at https://phylobone.com ) includes 255 proteins potentially expressed in the bone extracellular matrix (ECM) of humans and 30 species of vertebrates. A bioinformatics pipeline was used to identify the evolutionary relationships of bone ECM proteins. The analysis facilitated the identification of potential model organisms to study the molecular mechanisms of bone regeneration. A network analysis showed high connectivity of bone ECM proteins. A total of 214 functional protein domains were identified, including collagen and the domains involved in bone formation and resorption. Information from public drug repositories was used to identify potential repurposing of existing drugs. The Phylobone database provides a platform to study bone regeneration and osteoporosis in light of (biological) evolution, and will substantially contribute to the identification of molecular mechanisms and drug targets.

Reading impairment after neonatal hypoglycemia with parieto-temporo-occipital injury without cortical blindness: A case report.

BACKGROUND: Perinatal brain injury may lead to later neurodevelopmental disorders, whose outcomes may vary due to neuroplasticity in young children. Recent neuroimaging studies have shown that the left parietotemporal area (which includes the left inferior parietal lobe) is associated with phonological awareness and decoding skills, which are essential skills for reading acquisition in children. However, the literature on the effect of perinatal cerebral injury on the development of phonological awareness or decoding ability in childhood is limited. CASE SUMMARY: We report the case of an 8-year-old boy who presented with reading difficulty following a perinatal injury in the parieto-temporal-occipital lobes. The patient was born at term and was treated for hypoglycemia and seizures during the neonatal period. Diffusion-weighted brain magnetic resonance imaging on postnatal day 4 revealed cortical and subcortical hyperintensities in the parieto-temporo-occipital lobe. At the age of 8 years, physical examination was unremarkable, aside from mild clumsiness. Despite occipital lobe injury, the patient had adequate visual acuity, normal eye movement, and no visual field defects. Full-scale intelligence quotient and verbal comprehension index on Wechsler Intelligence Scale for Children-Fourth Edition were 75 and 90, respectively. Further assessment revealed adequate recognition of Japanese Hiragana letters. However, he had significantly slower reading speed in the Hiragana reading test than control children. The phonological awareness test revealed significant errors (standard deviation +2.7) in the mora reversal task. CONCLUSION: Patients with perinatal brain injuries in the parietotemporal area require attention and may benefit from additional reading instructions.

Inter-Laboratory Study on Measuring the Surface Charge of Electrically Polarized Hydroxyapatite.

Surface charges on implants improve integration into bone and so require a clear protocol for achieving a surface charge and comparable results from different laboratories. This study sintered hydroxyapatite (HAp) at one laboratory to remove the influence of the microstructure on surface charge and then polarized/depolarized the pellets at two different laboratories (in Tokyo and Riga). Surface charges on HAp pellets induced by electric polarization at 400 °C in a 5 kV/cm DC electric field were measured by the thermally stimulated depolarization current (TSDC) method as 6-9 µC/cm2. The surface charge results were comparable between laboratories and also agreed with previously documented values. Recommendations describe conditions for polarization and depolarization to generate a surface charge and repeatedly achieve a comparable outcome. A visual display of the polarization mechanisms and the contribution to surface charge point to further aspects that need further development.

Prevalence and Prognostic Significance of Malnutrition in Older Japanese Adults at High Surgical Risk Undergoing Transcatheter Aortic Valve Implantation.

Background The usefulness of preprocedural nutritional status to stratify prognosis after transcatheter aortic valve implantation has been evaluated; however, the studies conducted so far have been relatively small and/or focused on a single nutritional index. This study sought to assess the prevalence and prognostic impact of malnutrition in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation. Methods and Results We applied the Controlling Nutritional Status score, Geriatric Nutritional Risk Index, and Prognostic Nutritional Index to 1040 consecutive older Japanese patients at high surgical risk who underwent transcatheter aortic valve implantation. According to the Controlling Nutritional Status score, Geriatric Nutritional Risk Index, and Prognostic Nutritional Index, 16.6%, 60.5%, and 13.8% patients had moderate or severe malnutrition, respectively; 89.3% were at least mildly malnourished by at least 1 score. Worse nutritional status was associated with older age, lower body mass index, higher degree of frailty, worse symptoms and renal function, atrial fibrillation, and anemia. During a median follow-up of 986 days (interquartile range, 556-1402 days), 273 (26.3%) patients died. Compared with normal nutrition, malnutrition was associated with an increased risk for all-cause death (adjusted hazard ratio for moderate and severe malnutrition, respectively: 2.19 (95% CI, 1.45-3.31; P<0.001) and 6.13 (95% CI, 2.75-13.70; P<0.001) for the Controlling Nutritional Status score, 2.02 (95% CI, 1.36-3.02; P=0.001) and 3.24 (95% CI, 1.86-5.65; P<0.001) for the Geriatric Nutritional Risk Index, and 1.60 (95% CI, 1.06-2.39; P=0.024) and 2.32 (95% CI, 1.50-3.60; P<0.001) for the Prognostic Nutritional Index). Conclusions Malnutrition is common in patients undergoing transcatheter aortic valve implantation and is associated with increased mortality.

Acute mitral regurgitation after non-ischemic papillary muscle rupture: A case report.

Papillary muscle rupture (PMR) is a life-threatening cardiac emergency that is generally associated with inadequate myocardial perfusion after acute myocardial infarction. Nonischemic spontaneous PMR occurs less frequently and is mostly caused by myocarditis, infections, or trauma. We report a patient with spontaneous PMR resulting in severe mitral regurgitation with refractory heart failure showing no specific causes but deterioration of the mitral leaflet and papillary muscle. The integration of pathologic and echocardiographic findings describes the details of the disease. .

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.

Initial trough concentration may be beneficial in preventing linezolid-induced thrombocytopenia.

We assessed whether prospective therapeutic drug monitoring to optimise the therapeutic range could prevent linezolid-induced thrombocytopenia. This prospective interventional study was conducted from September 2017 to October 2020 among 37 adult patients receiving linezolid. Patients were administered one of the following two initial dosages: 600 mg twice or once daily for patients with a creatinine clearance rate of ≥50 or <50 mL/min, respectively. Linezolid dosage adjustment was performed on days 3-5 based on the trough concentration. The serum linezolid levels in 22 and 15 patients were within and above the therapeutic range (2-7 µg/mL), respectively. The incidence of thrombocytopenia was significantly lower among patients whose linezolid levels were within the therapeutic range (4.5%;1/22) than in those whose levels were above the therapeutic range (80%; 12/15). It is important to maintain the linezolid level within the therapeutic range at the first therapeutic drug monitoring to prevent thrombocytopenia.

Initial practice of left atrial appendage closure device in Japan; single-center experience.

BACKGROUND: The left atrial appendage closure (LAAC) device for patients with nonvalvular atrial fibrillation (NVAF) has recently been introduced in Japan. However, clinical data of Japanese patients are insufficient. METHODS: In this single-center study, 55 consecutive patients (mean age, 74 years) who received LAAC therapy from September 2019 to December 2020 were analyzed. The WATCHMAN implant procedure (Boston Scientific, St. Paul, MN, USA) was performed under transesophageal echocardiography and general anesthesia for all cases. RESULTS: The baseline CHA2DS2-VASc score was 4.6 ± 1.4, and the baseline HAS-BLED score was 3.8 ± 0.9. All procedures (98.2%) were successful, except for one, and no procedure-related complications were observed. After the procedures, various antithrombotic regimens were employed according to the bleeding risk of each patient; warfarin was used in 27 patients (49%), direct oral anticoagulants (DOACs) were used in 22 patients (40%), and dual antiplatelet therapy (DAPT) was employed in 6 patients. During a mean follow-up of 360 days, three cases of device-related thrombus (DRT) were detected. One DRT case was related to ischemic stroke. Nine patients had major bleeding during follow-up: two patients received DOACs, six patients received DAPT, and one patient received aspirin. CONCLUSIONS: In this initial Japanese experience, LAAC therapy for high bleeding risk patients with NVAF seems feasible. Optimal antithrombotic regimens are warranted for better clinical outcomes.

Surface Electric Fields Increase Human Osteoclast Resorption through Improved Wettability on Carbonate-Incorporated Apatite.

Osteoclast-mediated bioresorption can be an efficient means of incorporating the dissolution of biomaterials in the bone remodeling process. Because of the compositionally and structurally close resemblance of biomaterials with the natural mineral phases of the bone matrix, synthetic carbonate-substituted apatite (CA) is considered as an ideal biomaterial for clinical use. The present study therefore investigated the effects of electrical polarization on the surface characteristics and interactions with human osteoclasts of hydroxyapatite (HA) and CA. Electrical polarization was found to improve the surface wettability of these materials by increasing the surface free energy, and this effect was maintained for 1 month. Analyses of human osteoclast cultures established that CA subjected to a polarization treatment enhanced osteoclast resorption but did not affect the early differentiation phase or the adherent morphology of the osteoclasts as evaluated by staining. These data suggest that the surface characteristics of the CA promoted osteoclast resorption. The results of this work are expected to contribute to the future design of cell-mediated bioresorbable biomaterials capable of resorption by osteoclasts and of serving as a scaffold for bone regeneration.