High-Throughput Bioprinting Method for Modeling Vascular Permeability in Standard Six-well Plates with Size and Pattern Flexibility.

Vascular permeability is a key factor in developing therapies for disorders associated with compromised endothelium, such as endothelial dysfunction in coronary arteries and impaired function of the blood-brain barrier. Existing fabrication techniques do not adequately replicate the geometrical variation in vascular networks in the human body, which substantially influences disease progression; moreover, these techniques often involve multi-step fabrication procedures that hinder the high-throughput production necessary for pharmacological testing. This paper presents a bioprinting protocol for creating multiple vascular tissues with desired patterns and sizes directly on standard six-well plates, overcoming existing resolution and productivity challenges in bioprinting technology. A simplified fabrication approach was established to construct six hollow, perfusable channels within a hydrogel, which were subsequently lined with human umbilical vein endothelial cells to form a functional and mature endothelium. The computer-controlled nature of 3D bioprinting ensures high reproducibility and requires fewer manual fabrication steps than traditional methods. This highlights VOP's potential as an efficient high-throughput platform for modeling vascular permeability and advancing drug discovery.

Impact of Accidental High or Low Implantation Depth on Peri-Procedural Outcomes after Implantation with the Self-Expanding ACURATE neo2.

Background: Precise implantation could play a crucial role in the technical success of transcatheter aortic valve replacement (TAVR) for some prostheses. The impact of an accidental implantation depth (ID) outside the recommended range has not been assessed for the ACURATE neo2 (NEO2). Methods: Data from 1839 patients with severe native aortic stenosis treated with the NEO2 prosthesis were evaluated. We compared the results of prostheses implanted in an ID both inside and outside the recommendations. The outcome assessment followed the Valve Academic Research Consortium-3 criteria. Results: Patients were retrospectively divided into high (<3 mm; n = 412), optimal (3-7 mm; n = 1236), and low (>7 mm; n = 169) implantations. Technical success (94.7% vs. 94.7% vs. 91.7%, p = 0.296) and device success were high (90.1% vs. 89.3% vs. 84.6%, p = 0.112) without differences between groups. Rates of relevant paravalvular regurgitation (PVL; >mild or VinV due to PVL) were comparable (1.2% vs. 1.8% vs. 1.2%, p = 0.759). Even when hemodynamics were superior in the high-implantation group, with greater iEOA (1.01 cm2/m2 vs. 0.95 cm2/m2 vs. 0.92 cm2/m2, p < 0.001), spontaneous embolization or after post-dilatation was more common. Low implantation was associated with a higher rate of associated pacemaker implantation (PPI) (6.1% vs. 8.8% vs. 14.8%, p = 0.001). Conclusions: Implantation with the ACURATE neo2 showed excellent hemodynamic results, including low gradients and a small number of relevant PVL, in line with a high technical success rate that was irrespective of the ID. A favorable outcome can also be achieved in accidental low or high positions. Low implantation was associated with a higher rate of associated pacemaker implantation. Deliberately high implantation should be avoided due to the risk of embolization.

Enhanced Osteogenesis in 2D and 3D Culture Systems Using RGD Peptide and α-TCP Phase Transition within Alginate-Based Hydrogel.

Cell-laden hydrogels have been extensively investigated in various tissue engineering fields by their potential capacity to deposit numerous types of cells in a specific area. They are largely used in soft-tissue engineering applications because of their low mechanical strength. In addition, sodium alginate is well-known for its encapsulation, loading capacity and for being easily controllable; however, it lacks cell-binding ligands and hence the ability to adhere cells. In this study, it is aimed to enhance osteogenesis in cells encapsulated in alginate and improve its mechanical properties by introducing a synthetic peptide and calcium phosphate phase transition. To increase cell-hydrogel interactions and increasing cell viability, an RGD peptide is added to a photocrosslinkable methacrylate-modified alginate, and alpha-tricalcium phosphate (α-TCP) is added to the hydrogel to increase its mechanical strength via phase transition. Cell proliferation, growth, and differentiation are assessed in both 2D and 3D cell cultures. The addition of α-TCP significantly improved the mechanical properties of the hydrogel. Moreover, the RGD peptide and α-TCP showed a synergistic effect with significantly improved cell adhesion and osteogenesis in both 2D and 3D cell cultures. Therefore, the functional hydrogel developed in this study can potentially be used for bone tissue regeneration.

Coaxial bioprinting of a stentable and endothelialized human coronary artery-sized in vitro model.

Atherosclerosis accounts for two-thirds of deaths attributed to cardiovascular diseases, which continue to be the leading cause of mortality. Current clinical management strategies for atherosclerosis, such as angioplasty with stenting, face numerous challenges, including restenosis and late thrombosis. Smart stents, integrated with sensors that can monitor cardiovascular health in real-time, are being developed to overcome these limitations. This development necessitates rigorous preclinical trials on either animal models or in vitro models. Despite efforts being made, a suitable human-scale in vitro model compatible with a cardiovascular stent has remained elusive. To address this need, this study utilizes an in-bath bioprinting method to create a human-scale, freestanding in vitro model compatible with cardiovascular stents. Using a coaxial nozzle, a tubular structure of human coronary artery (HCA) size is bioprinted with a collagen-based bioink, ensuring good biocompatibility and suitable rheological properties for printing. We precisely replicated the dimensions of the HCA, including its internal diameter and wall thickness, and simulated the vascular barrier functionality. To simplify post-processing, a pumpless perfusion bioreactor is fabricated to culture a HCA-sized model, eliminating the need for a peristaltic pump and enabling scalability for high-throughput production. This model is expected to accelerate stent development in the future.

Bioinks for bioprinting using plant-derived biomaterials.

Three-dimensional (3D) bioprinting has revolutionized tissue engineering by enabling the fabrication of complex and functional human tissues and organs. An essential component of successful 3D bioprinting is the selection of an appropriate bioink capable of supporting cell proliferation and viability. Plant-derived biomaterials, because of their abundance, biocompatibility, and tunable properties, hold promise as bioink sources, thus offering advantages over animal-derived biomaterials, which carry immunogenic concerns. This comprehensive review explores and analyzes the potential of plant-derived biomaterials as bioinks for 3D bioprinting of human tissues. Modification and optimization of these materials to enhance printability and biological functionality are discussed. Furthermore, cancer research and drug testing applications of the use of plant-based biomaterials in bioprinting various human tissues such as bone, cartilage, skin, and vascular tissues are described. Challenges and limitations, including mechanical integrity, cell viability, resolution, and regulatory concerns, along with potential strategies to overcome them, are discussed. Additionally, this review provides insights into the potential use of plant-based decellularized ECM (dECM) as bioinks, future prospects, and emerging trends in the use of plant-derived biomaterials for 3D bioprinting applications. The potential of plant-derived biomaterials as bioinks for 3D bioprinting of human tissues is highlighted herein. However, further research is necessary to optimize their processing, standardize their properties, and evaluate their long-termin vivoperformance. Continued advancements in plant-derived biomaterials have the potential to revolutionize tissue engineering and facilitate the development of functional and regenerative therapies for diverse clinical applications.

Sex-specific survival gene mutations are discovered as clinical predictors of clear cell renal cell carcinoma.

Although sex differences have been reported in patients with clear cell renal cell carcinoma (ccRCC), biological sex has not received clinical attention and genetic differences between sexes are poorly understood. This study aims to identify sex-specific gene mutations and explore their clinical significance in ccRCC. We used data from The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma (TCGA-KIRC), The Renal Cell Cancer-European Union (RECA-EU) and Korean-KIRC. A total of 68 sex-related genes were selected from TCGA-KIRC through machine learning, and 23 sex-specific genes were identified through verification using the three databases. Survival differences according to sex were identified in nine genes (ACSS3, ALG13, ASXL3, BAP1, JADE3, KDM5C, KDM6A, NCOR1P1, and ZNF449). Female-specific survival differences were found in BAP1 in overall survival (OS) (TCGA-KIRC, p = 0.004; RECA-EU, p = 0.002; and Korean-KIRC, p = 0.003) and disease-free survival (DFS) (TCGA-KIRC, p = 0.001 and Korean-KIRC, p = 0.000004), and NCOR1P1 in DFS (TCGA-KIRC, p = 0.046 and RECA-EU, p = 0.00003). Male-specific survival differences were found in ASXL3 (OS, p = 0.017 in TCGA-KIRC; and OS, p = 0.005 in RECA-EU) and KDM5C (OS, p = 0.009 in RECA-EU; and DFS, p = 0.016 in Korean-KIRC). These results suggest that biological sex may be an important predictor and sex-specific tailored treatment may improve patient care in ccRCC.

Donor-derived cell-free DNA predicted allograft rejection and severe microvascular inflammation in kidney transplant recipients.

Introduction: The aim of this study is to investigate the clinical validity of donor-derived cell-free DNA (dd-cfDNA) in comparison with that of donor specific anti-HLA antibody (DSA) for predicting biopsy-proven rejection (BPR)and severe microvascular inflammation (severe MVI) in kidney transplant recipients (KTRs). Methods: In this prospective observational investigation, 64 KTRs who underwent the indicated biopsies were included. Blood samples collected prior to biopsy were tested for dd-cfDNA and DSA. Biopsy specimens were classified by a renal pathologist according to the Banff classification. The predictive performance of dd-cfDNA and DSA for histological allograft diagnosis was assessed. Results: KTRs were categorized into the high and low dd-cfDNA groups based on a level of 0.4%. Eighteen patients (28.1%) had positive DSA at biopsy, exhibiting higher dd-cfDNA levels than the DSA-negative patients. BPR and severe MVI incidences were elevated in the high dd-cfDNA group (BPR: 42.9% vs. 3.4%, P <0.001; severe MVI: 37.1% vs. 3.4%, P = 0.001). Also, elevated glomerulitis and MVI scores were observed in the high dd-cfDNA group. DSA showed the highest predictive value for BPR (AUC = 0.880), whereas dd-cfDNA alone excelled in predicting severe MVI (AUC = 0.855). Combination of DSA and dd-cfDNA (>0.4%) yielded sensitivities of 80.0% and 50.0% with specificities of 90.7% and 88.0% for antibody-mediated rejection and severe MVI detection, respectively. Conclusion: The dd-cfDNA test is a predictive tool for BPR and severe MVI, and it can improve the performance, especially when combined with DSA for BPR.

Composition control of additively manufactured color-graded temporary veneer.

OBJECTIVE: The aim of this study was to design and assess composite resin composition for patient-specific esthetic color-graded temporary veneer. METHODS: Various compositions of composite structures (assorted by Ba2SiO4 filler, TiO2 pigment, and photoinitiator) were prepared via additive manufacturing with 3 s UV exposure (405 nm, 10 W/cm2) per 50 µm thick layer followed by 20 min post-curing treatment after fabrication. The effect of each component on the generated color shades was observed and compared to the commonly used VITA shade guide. The coloration was explored by staining aging treatment under dry, wet, artificial saliva environments, coffee, and cola. The mechanical properties were also evaluated. Color measurement and comparison were done using a colorimeter (lightness (L*), green-red color (a*), and blue-yellow color (b*)), and the changes were calculated by CIEDE2000 (ΔE00), translucency parameter (TP) and whiteness index (WID). The composition color analysis results were then applied to produce a color-graded temporary veneer for mimicking a natural look. RESULT: Mechanically, all composition result in adequate bending strength with maximum achievable strength of 111.64 MPa. At the same time, the composite color was affected by each constituent differently. The L* value, which indicates the color lightness of the composite, was considerably tuned by the TiO2 pigment, whereas Ba2SiO4 filler only triggered minor changes. Photoinitiator concentration significantly affected the yellowness, indicated by the increased b* value. Similar tendency also observed toward the calculated TP and WID as well. Based on these evaluations, color-graded temporary veneer successfully generated, matching the VITA A3, A2, and B1 shades gradation. However, the stability of the composite color decreased at high amounts of Ba2SiO4 and photoinitiator. SIGNIFICANCE: The study presents a composition guide for fabricating temporary patient-specific color-graded veneer. It provides insights on the effect of the constituent material on dental esthetics.

Discovery and Validation of Survival-Specific Genes in Papillary Renal Cell Carcinoma Using a Customized Next-Generation Sequencing Gene Panel.

PURPOSE: Papillary renal cell carcinoma (PRCC), the second most common kidney cancer, is morphologically, genetically, and molecularly heterogeneous with diverse clinical manifestations. Genetic variations of PRCC and their association with survival are not yet well-understood. This study aimed to identify and validate survival-specific genes in PRCC and explore their clinical utility. MATERIALS AND METHODS: Using machine learning, 293 patients from the Cancer Genome Atlas-Kidney Renal Papillary Cell Carcinoma (TCGA-KIRP) database were analyzed to derive genes associated with survival. To validate these genes, DNAs were extracted from the tissues of 60 Korean PRCC patients. Next generation sequencing was conducted using a customized PRCC gene panel of 202 genes, including 171 survival-specific genes. Kaplan-Meier and Log-rank tests were used for survival analysis. Fisher's exact test was performed to assess the clinical utility of variant genes. RESULTS: A total of 40 survival-specific genes were identified in the TCGA-KIRP database through machine learning and statistical analysis. Of them, 10 (BAP1, BRAF, CFDP1, EGFR, ITM2B, JAK1, NODAL, PCSK2, SPATA13, and SYT5) were validated in the Korean-KIRP database. Among these survival gene signatures, three genes (BAP1, PCSK2, and SPATA13) showed survival specificity in both overall survival (OS) (p = 0.00004, p = 1.38 × 10-7, and p = 0.026, respectively) and disease-free survival (DFS) (p = 0.00002, p = 1.21 × 10-7, and p = 0.036, respectively). Notably, the PCSK2 mutation demonstrated survival specificity uniquely in both the TCGA-KIRP (OS: p = 0.010 and DFS: p = 0.301) and Korean-KIRP (OS: p = 1.38 × 10-7 and DFS: p = 1.21 × 10-7) databases. CONCLUSIONS: We discovered and verified genes specific for the survival of PRCC patients in the TCGA-KIRP and Korean-KIRP databases. The survival gene signature, including PCSK2 commonly obtained from the 40 gene signature of TCGA and the 10 gene signature of the Korean database, is expected to provide insight into predicting the survival of PRCC patients and developing new treatment.

Surgical Outcomes of Revision Orbital Reconstruction in Patients With Inadequate Primary Orbital Fracture Repair.

OBJECTIVE: This study aimed to investigate the clinical characteristics of patients with complications following inadequate primary orbital fracture repair and to evaluate surgical outcomes of secondary revision orbital reconstruction. METHODS: The authors retrospectively reviewed data from 41 patients who underwent revision orbital reconstruction by a single surgeon following complications from primary orbital fracture repair performed elsewhere. Clinical characteristics, including enophthalmos, exophthalmos, diplopia, ocular motility limitation, epiphora, infraorbital hypoesthesia, infection, eyelid malposition, lagophthalmos, hypoglobus, and compressive optic neuropathy, were assessed. Surgical outcomes of revision surgery were evaluated to determine improvements in clinical deficits and postoperative patient satisfaction. RESULTS: The most common postoperative complications of primary orbital fracture repair were enophthalmos (n=20/41) and diplopia (n=20/41). The mean time between primary and revision surgeries was 67.2 months (range: 1-276 mo). Revision surgery significantly improved enophthalmos, diplopia (Hess area ratio), epiphora (Munk score), periorbital pain, and exophthalmos ( P =0.003, P =0.001, P <0.001, P <0.001, and P =0.007, respectively) compared to the pre-revision state. In addition, 6 patients experienced improved infraorbital hypoesthesia. Among the 41 patients, 23 were very satisfied, 17 were satisfied, and 1 was neutral after revision orbital reconstruction. CONCLUSIONS: Our study highlights the positive impact of revision orbital reconstruction in addressing complications from inadequate primary orbital fracture repair. Surgeons should consider revision surgery to address clinical deficits following prior surgery, especially when anatomic abnormalities are evident in imaging studies, regardless of the time lapse since the initial surgery or concerns about tissue fibrosis and fat atrophy.

Crusting-fabricated three-dimensional soy-based scaffolds for cultured meat production: A preliminary study.

Crusting has been developed as a non-chemical and non-machine intensive scaffold fabrication method. This method is based on the self-assembling ability of soy biomolecules, allowing the fabrication of a three-dimensional network for cell growth. Preliminary characterization revealed differences in pore size, water absorption, and degradation between pure soy-based scaffold (Y2R) and with added glycerol (Y2G). The Fourier-transform infrared spectrum absorbance peaks of functional groups related to proteins, carbohydrates, and lipids hinted the integration of soy biomolecules potentially via the Maillard reaction, as supported by the visible browning of the scaffold surface. Microscopic images revealed aligned myotubes in both scaffolds, with Y2G myotubes having greater proximity after 72 h of proliferation. Both spontaneous and electro-stimulated contractions were recorded as early as 72 h in proliferation medium. Crusting-fabricated soy-based scaffolds can further be explored for its application in cultured meat production.

Myrosinase isogenes in wasabi (Wasabia japonica Matsum) and their putative roles in glucosinolate metabolism.

BACKGROUND: Wasabi, a Brassicaceae member, is well-known for its unique pungent and hot flavor which is produced from glucosinolate (GSL) degradation. Myrosinase (MYR) is a principle enzyme catalyzing the primary conversion of GSLs to GSL hydrolysis products (GHPs) which is responsible for plant defense system and food quality. Due to the limited information in relation to MYRs present in wasabi (Wasabia japonica M.), this study aimed to identify the MYR isogenes in W. japonica and analyze their roles in relation to GSL metabolism. RESULTS: In results, WjMYRI-1 was abundantly expressed in all organs, whereas WjMYRI-2 showed only trace expression levels. WjMYRII was highly expressed in the aboveground tissues. Interestingly, WjMYRII expression was significantly upregulated by certain abiotic factors, such as methyl jasmonate (more than 40-fold in petioles and 15-fold in leaves) and salt (tenfold in leaves). Young leaves and roots contained 97.89 and 91.17 µmol‧g-1 of GSL, whereas less GSL was produced in mature leaves and petioles (38.36 and 44.79 µmol‧g-1, respectively). Similar pattern was observed in the accumulation of GHPs in various plant organs. Notably, despite the non-significant changes in GSL production, abiotic factors treated samples enhanced significantly GHP content. Pearson's correlation analysis revealed that WjMYRI-1 expression significantly correlated with GSL accumulation and GHP formation, suggesting the primary role of WjMYRI-1-encoding putative protein in GSL degradation. In contrast, WjMYRII expression level showed no correlation with GSL or GHP content, suggesting another physiological role of WjMYRII in stress-induced response. CONCLUSIONS: In conclusions, three potential isogenes (WjMYRI-1, WjMYRI-2, and WjMYRII) encoding for different MYR isoforms in W. japonica were identified. Our results provided new insights related to MYR and GSL metabolism which are important for the implications of wasabi in agriculture, food and pharmaceutical industry. Particularly, WjMYRI-1 may be primarily responsible for GSL degradation, whereas WjMYRII (clade II) may be involved in other regulatory pathways induced by abiotic factors.

Patient-Reported Postoperative Neuropsychological Deterioration After Heart Valve Replacement and Coronary Artery Bypass Grafting.

Background: Postoperative cognitive decline (POCD) after cardiosurgical interventions are well described through objective psychometric tests. However, a patient's subjective perception is essential to clinical assessment and quality of life. This study systematically evaluated patient-reported POCD between subjects undergoing coronary artery bypass grafting and heart valve replacement. Methods: This study was a multicentre, prospective questionnaire survey conducted at the cardiac surgery departments at the Kerckhoff Clinic in Bad Nauheim and the University Hospital in Giessen, Germany. We included patients undergoing elective coronary artery bypass grafting (CABG), aortic valve replacement (AVR), mitral valve replacement or reconstruction (MVR), and combined surgery (CABG + valve replacement [VR]) with extracorporeal circulation. The Hospital Anxiety and Depression Scale, the Cognitive Failures Questionnaire (CFQ) for Self-assessment (CFQ-S), and the external assessment (CFQ-foreign [F]) were completed preoperatively, as well as at 3 and 12 months postoperatively. Results: A total of 491 patients were available for analyses (CABG = 182, AVR = 134, MVR = 93, CABG + VR = 82). POCD and postoperative depression increase (PODI) were observed for each surgical procedure. (At the 3-month follow-up: CFQ-S [CABG = 7.1%, AVR = 3.7%, MVR = 9.7%, CABG + VR = 9.8%]; CFQ-F [CABG = 9.9%, AVR = 9.7%, MVR = 9.7%, CABG + VR = 15.9%]; PODI [CABG = 7.7%, AVR = 9.7%, MVR = 6.5%, CABG + VR = 8.5%]. At the 12-month follow-up: CFQ-S [CABG = 6.6%, AVR = 7.5%, MVR = 15.1%, CABG + VR = 7.3%]; CFQ-F [CABG = 7.1%, AVR = 14.9%, MVR = 10.8%, CABG + VR = 9.8%]; PODI [CABG = 10.4%, AVR = 11.2%, MVR = 6.5%, CABG + VR = 4.9%]). No significant between-group effects were observed for the CFQ-S, CFQ-F, or the Hospital Anxiety and Depression Scale. Conclusions: For clinicians, paying attention to patients' self-reported experiences of reduced cognitive function and symptoms of depression following cardiac surgery is important. Such reporting is an indication that interventions such as cognitive training or psychotherapy should be considered.

Contexte: Le déclin cognitif postopératoire (DCPO) à la suite d'interventions de chirurgie cardiaque est bien décrit par des évaluations psychométriques objectives. Cependant, la perception subjective du patient est essentielle à l'évaluation clinique et à la qualité de vie. Cette étude visait à évaluer de façon systématique le DCPO déclaré par le patient chez des sujets ayant subi un pontage aortocoronarien ou une chirurgie valvulaire. Méthodologie: Cette étude prospective multicentrique par questionnaire a été menée aux services de chirurgie cardiaque de la clinique Kerckhoff de Bad Nauheim et de l'hôpital universitaire de Giessen, en Allemagne. Elle a porté sur des patients ayant subi un pontage aortocoronarien (PAC), un remplacement valvulaire aortique (RVA), un remplacement ou une reconstruction de la valvule mitrale (RVM) ou une chirurgie combinée (PAC et remplacement valvulaire [RV]) avec circulation extracorporelle, en situation non urgente. L'échelle d'évaluation de l'anxiété et de la dépression à l'hôpital (HADS), le questionnaire d'auto-évaluation des déficits cognitifs (CFQ-S) et le questionnaire d'évaluation externe des déficits cognitifs (CFQ-F) ont été remplis avant l'intervention chirurgicale, ainsi que 3 et 12 mois après la chirurgie. Résultats: Au total, les résultats de 491 patients étaient disponibles aux fins d'analyses (PAC = 182, RVA = 134, RVM = 93, PAC et RV = 82). Des cas de DCPO et une augmentation postopératoire des symptômes de dépression (APOD) ont été observés après chacune des interventions chirurgicales. (Lors du suivi après 3 mois : DCPO selon le CFQ-S [PAC = 7,1 %, RVA = 3,7 %, RVM = 9,7 %, PAC + RV = 9,8 %]; DCPO selon le CFQ-F [PAC = 9,9 %, RVA = 9,7 %, RVM = 9,7 %, PAC + RV = 15,9 %]; APOD [PAC = 7,7 %, RVA = 9,7 %, RVM = 6,5 %, PAC + RV = 8,5 %]. Lors du suivi après 12 mois : DCPO selon le CFQ-S [PAC = 6,6 %, RVA = 7,5 %, RVM = 15,1 %, PAC + RV = 7,3 %]; DCPO selon le CFQ-F [PAC= 7,1 %, RVA = 14,9 %, RVM = 10,8 %, PAC+ RV = 9,8 %]; APOD [PAC = 10,4 %, RVA = 11,2 %, RVM = 6,5 %, PAC + RV = 4,9 %]). Aucun effet intergroupe significatif n'a été observé relativement aux questionnaires CFQ-S et CFQ-F ou à l'échelle HADS. Conclusions: Il est important que les cliniciens portent attention aux déclarations des patients en ce qui concerne la diminution des fonctions cognitives et les symptômes de dépression à la suite d'une chirurgie cardiaque. De telles déclarations sont une indication que des interventions comme l'entraînement cognitif ou la psychothérapie doivent être envisagées.

Transcatheter or Surgical Treatment of Aortic-Valve Stenosis.

BACKGROUND: Among low-risk patients with severe, symptomatic aortic stenosis who are eligible for both transcatheter aortic-valve implantation (TAVI) and surgical aortic-valve replacement (SAVR), data are lacking on the appropriate treatment strategy in routine clinical practice. METHODS: In this randomized noninferiority trial conducted at 38 sites in Germany, we assigned patients with severe aortic stenosis who were at low or intermediate surgical risk to undergo either TAVI or SAVR. Percutaneous- and surgical-valve prostheses were selected according to operator discretion. The primary outcome was a composite of death from any cause or fatal or nonfatal stroke at 1 year. RESULTS: A total of 1414 patients underwent randomization (701 to the TAVI group and 713 to the SAVR group). The mean (±SD) age of the patients was 74±4 years; 57% were men, and the median Society of Thoracic Surgeons risk score was 1.8% (low surgical risk). The Kaplan-Meier estimate of the primary outcome at 1 year was 5.4% in the TAVI group and 10.0% in the SAVR group (hazard ratio for death or stroke, 0.53; 95% confidence interval [CI], 0.35 to 0.79; P<0.001 for noninferiority). The incidence of death from any cause was 2.6% in the TAVI group and 6.2% in the SAVR group (hazard ratio, 0.43; 95% CI, 0.24 to 0.73); the incidence of stroke was 2.9% and 4.7%, respectively (hazard ratio, 0.61; 95% CI, 0.35 to 1.06). Procedural complications occurred in 1.5% and 1.0% of patients in the TAVI and SAVR groups, respectively. CONCLUSIONS: Among patients with severe aortic stenosis at low or intermediate surgical risk, TAVI was noninferior to SAVR with respect to death from any cause or stroke at 1 year. (Funded by the German Center for Cardiovascular Research and the German Heart Foundation; DEDICATE-DZHK6 ClinicalTrials.gov number, NCT03112980.).

[Catheter-based and surgical treatment for aortic valve diseases]. / Katheterbasierte und operative Therapie bei Aortenvitien.

The pathophysiology of aortic valve diseases is of predominantly degenerative nature, characterized by calcific aortic valve stenosis, which is associated with a reduction in prognosis. The prevalence of aortic valve insufficiency also increases with advancing age. Timely causal treatment is crucial in the management of aortic valve diseases. Following the indication for intervention, the heart team plays a central role in evaluating the results and making therapeutic decisions that consider the patient's preferences. In the assessment of treatment options, considerations regarding the long-term perspective are particularly crucial, especially in younger patients. The most common therapeutic approach for aortic valve diseases is the introduction of a new valve prosthesis. In the majority of cases, this is now achieved through catheter-based implantation of a bioprosthetic heart valve, known as transcatheter aortic valve implantation (TAVI). Open surgical aortic valve replacement (AVR) is favored in younger patients with low surgical risk or in the case that TAVI is not feasible. In AVR, both biological and the longest-lasting mechanical prosthesis types are used. Surgical repair techniques are primarily applied in cases of aortic valve regurgitation. Notably, TAVI, as well as surgical procedures for the treatment of aortic valve diseases, have undergone significant advancements in recent years, including expanded indications for TAVI and, on the surgical side, in particular the development of minimally invasive surgical techniques.

Plant-Based Decellularization: A Novel Approach for Perfusion-Compatible Tissue Engineering Structures.

This study explores the potential of plant-based decellularization in regenerative medicine, a pivotal development in tissue engineering focusing on scaffold development, modification, and vascularization. Plant decellularization involves removing cellular components from plant structures, offering an eco-friendly and cost-effective alternative to traditional scaffold materials. The use of plant-derived polymers is critical, presenting both benefits and challenges, notably in mechanical properties. Integration of plant vascular networks represents a significant bioengineering breakthrough, aligning with natural design principles. The paper provides an in-depth analysis of development protocols, scaffold fabrication considerations, and illustrative case studies showcasing plant-based decellularization applications. This technique is transformative, offering sustainable scaffold design solutions with readily available plant materials capable of forming perfusable structures. Ongoing research aims to refine protocols, assess long-term implications, and adapt the process for clinical use, indicating a path toward widespread adoption. Plant-based decellularization holds promise for regenerative medicine, bridging biological sciences with engineering through eco-friendly approaches. Future perspectives include protocol optimization, understanding long-term impacts, clinical scalability, addressing mechanical limitations, fostering collaboration, exploring new research areas, and enhancing education. Collectively, these efforts envision a regenerative future where nature and scientific innovation converge to create sustainable solutions, offering hope for generations to come.

Atypical post-infectious glomerulonephritis with c-ANCA positivity followed by endocarditis.

Post-infectious glomerulonephritis (PIGN), an uncommon variety of glomerulonephritis (GN), is characterized by emergence of nephritic syndrome within a few weeks following an infectious event. PIGN typically presents as a mild condition and tends to resolve by the time of diagnosis for GN. Aggregatibacter actinomycetemcomitans belongs to the HACEK group of bacteria, which constitutes less than 3% of bacteria responsible for community-acquired infective endocarditis. We present a case of 29-year-old man suspected of lymphoma with B-symptoms along with severe splenomegaly and nephromegaly. Shortly after, he developed an episode of nephritic syndrome accompanied by acute kidney injury (AKI) and high titers of cytoplasmic ANCA (c-ANCA)-positivity. Kidney biopsy revealed PIGN with tubulointerstitial nephritis. Despite treatment with antibiotics and corticosteroid, he visited the emergency room due to worsening dyspnea and multi-organ failure. An echocardiogram showed a bicuspid aortic valve with vegetation unseen on previous echocardiogram. He underwent aortic valve replacement immediately without adverse events. Four months after valve replacement, his renal function and cardiac performance have remained stable. We report a case of PIGN with AKI and high titers of c-ANCA appearing later as an infective endocarditis due to Aggregatibacter actinomycetemcomitans. With careful clinical observation and appropriate and timely management, satisfactory outcomes for patient health are possible.

CoFe2O4 on Mica Substrate as Flexible Ethanol Gas Sensor in Self-Heating Mode.

In this study, a novel flexible ethanol gas sensor was created by the deposition of a CoFe2O4 (CFO) thin film on a thin mica substrate using the pulsed laser deposition technique. Transition electron microscopy (TEM) investigations clearly demonstrated the successful growth of CFO on the mica, where a well-defined interface was observed. Ethanol gas-sensing studies showed optimal performance at 200 °C, with the highest response of 19.2 to 100 ppm ethanol. Operating the sensor in self-heating mode under 7 V applied voltage, which corresponds to a temperature of approximately 200 °C, produced a maximal response of 19.2 to 100 ppm ethanol. This aligned with the highest responses observed during testing at 200 °C, confirming the sensor's accuracy and sensitivity to ethanol under self-heating conditions. In addition, the sensor exhibited good selectivity to ethanol and excellent flexibility, maintaining its high performance after bending and tilting up to 5000 times. As this is the first report on flexible self-heated CFO gas sensors, we believe that this research holds great promise for the future development of high-quality sensors based on this approach.

ACURATE neo2 Versus SAPIEN 3 Ultra Transcatheter Heart Valve in Severe Aortic Valve Calcification: A Propensity-Matched Analysis.

BACKGROUND: Comparative data on transcatheter self-expanding ACURATE neo2 (NEO2) and balloon-expandable SAPIEN 3 Ultra prostheses in technically challenging anatomy of severe aortic valve calcified aortic annuli are scarce. METHODS: A total of 1987 patients with severe native aortic stenosis treated with the self-expanding NEO2 (n=1457) or balloon-expandable SAPIEN 3 Ultra (n=530) from January 2017 to April 2023 were evaluated. The primary end point was procedural outcome according to the Valve Academic Research Consortium 3 definitions. Propensity matching defined 219 pairs with severe calcification (calcium density cutoff, 758 AU/cm2) of the native aortic valve. RESULTS: Technical success (90.4% versus 91.8%; risk difference, 1.4% [95% CI, -4.4 to -7.2]; P=0.737) and device success at 30 days (80.8% versus 75.8%; risk difference, -5.0% [95% CI, -13.2 to 3.1]; P=0.246) were comparable between NEO2 and SAPIEN 3 Ultra. The rate of severe prosthesis-patient mismatch (1.1% versus 10.1%; risk difference, 10.0% [95% CI, 4.0-13.9]; P<0.001) and mean transvalvular gradient ≥20 mm Hg (2.8% versus 14.3%; risk difference, 11.5% [95% CI, 5.8-17.1]; P<0.001) was lower with NEO2. The rate of more-than-mild paravalvular leakage or valve-in-valve due to paravalvular leakage was significantly higher (6.2% versus 0.0%; risk difference, 6.2% [95% CI, -10.1 to -2.7]; P=0.002), and there was a tendency for a higher rate of device embolization or migration (1.8% versus 0.0%; risk difference, -1.8% [95% CI, -4.1 to 0.4]; P=0.123) with NEO2. Multivarate regression revealed no independent impact of transcatheter heart valve selection on device success (odds ratio, 0.93 [95% CI, 0.48-1.77]; P=0.817). CONCLUSIONS: In patients with severely calcified annuli, supraannular implantation of NEO2 showed hemodynamic advantages. Nevertheless, NEO2 was associated with a higher incidence of relevant paravalvular leakage and a numerically higher rate of device embolization than SAPIEN 3 Ultra in this particular patient group.