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Search Results (349)

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Keywords = three-vessel disease

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9 pages, 203 KiB  
Article
Minimally Invasive Off-Pump Coronary Artery Bypass as Palliative Revascularization in High-Risk Patients
by Magdalena Rufa, Adrian Ursulescu, Samir Ahad, Ragi Nagib, Marc Albert, Rafael Ayala, Nora Göbel, Tunjay Shavahatli, Mihnea Ghinescu, Ulrich Franke and Bartosz Rylski
Clin. Pract. 2025, 15(8), 147; https://doi.org/10.3390/clinpract15080147 - 6 Aug 2025
Abstract
Background: In high-risk and frail patients with multivessel coronary artery disease (MV CAD), guidelines indicated complete revascularization with or without the use of cardiopulmonary bypass (CPB) bears a high morbidity and mortality risk. In cases where catheter interventions were deemed unsuitable and conventional [...] Read more.
Background: In high-risk and frail patients with multivessel coronary artery disease (MV CAD), guidelines indicated complete revascularization with or without the use of cardiopulmonary bypass (CPB) bears a high morbidity and mortality risk. In cases where catheter interventions were deemed unsuitable and conventional coronary artery bypass grafting (CABG) posed an unacceptable perioperative risk, patients were scheduled for minimally invasive direct coronary artery bypass (MIDCAB) grafting or minimally invasive multivessel coronary artery bypass grafting (MICS-CABG). We called this approach “palliative revascularization.” This study assesses the safety and impact of palliative revascularization on clinical outcomes and overall survival. Methods: A consecutive series of 57 patients undergoing MIDCAB or MICS-CABG as a palliative surgery between 2008 and 2018 was included. The decision for palliative surgery was met in heart team after carefully assessing each case. The patients underwent single or double-vessel revascularization using the left internal thoracic artery and rarely radial artery/saphenous vein segments, both endoscopically harvested. Inpatient data could be completed for all 57 patients. The mean follow-up interval was 4.2 ± 3.7 years, with a follow-up rate of 91.2%. Results: Mean patient age was 79.7 ± 7.4 years. Overall, 46 patients (80.7%) were male, 26 (45.6%) had a history of atrial fibrillation and 25 (43.9%) of chronic kidney disease. In total, 13 patients exhibited a moderate EuroSCORE II, while 27 were classified as high risk, with a EuroSCORE II exceeding 5%. Additionally, 40 patients (70.2%) presented with three-vessel disease, 17 (29.8%) suffered an acute myocardial infarction within three weeks prior to surgery and 50.9% presented an impaired ejection fraction. There were 48 MIDCAB and nine MICS CABG with no conversions either to sternotomy or to CPB. Eight cases were planned as hybrid procedures and only 15 patients (26.3%) were completely revascularized. During the first 30 days, four patients (7%) died. A myocardial infarction occurred in only one case, no patient necessitated immediate reoperation. The one-, three- and five-year survival rates were 83%, 67% and 61%, respectively. Conclusions: MIDCAB and MICS CABG can be successfully conducted as less invasive palliative surgery in high-risk multimorbid patients with MV CAD. The early and mid-term results were better than predicted. A higher rate of hybrid procedures could improve long-term outcome in selected cases. Full article
24 pages, 1471 KiB  
Article
WDM-UNet: A Wavelet-Deformable Gated Fusion Network for Multi-Scale Retinal Vessel Segmentation
by Xinlong Li and Hang Zhou
Sensors 2025, 25(15), 4840; https://doi.org/10.3390/s25154840 - 6 Aug 2025
Abstract
Retinal vessel segmentation in fundus images is critical for diagnosing microvascular and ophthalmologic diseases. However, the task remains challenging due to significant vessel width variation and low vessel-to-background contrast. To address these limitations, we propose WDM-UNet, a novel spatial-wavelet dual-domain fusion architecture that [...] Read more.
Retinal vessel segmentation in fundus images is critical for diagnosing microvascular and ophthalmologic diseases. However, the task remains challenging due to significant vessel width variation and low vessel-to-background contrast. To address these limitations, we propose WDM-UNet, a novel spatial-wavelet dual-domain fusion architecture that integrates spatial and wavelet-domain representations to simultaneously enhance the local detail and global context. The encoder combines a Deformable Convolution Encoder (DCE), which adaptively models complex vascular structures through dynamic receptive fields, and a Wavelet Convolution Encoder (WCE), which captures the semantic and structural contexts through low-frequency components and hierarchical wavelet convolution. These features are further refined by a Gated Fusion Transformer (GFT), which employs gated attention to enhance multi-scale feature integration. In the decoder, depthwise separable convolutions are used to reduce the computational overhead without compromising the representational capacity. To preserve fine structural details and facilitate contextual information flow across layers, the model incorporates skip connections with a hierarchical fusion strategy, enabling the effective integration of shallow and deep features. We evaluated WDM-UNet in three public datasets: DRIVE, STARE, and CHASE_DB1. The quantitative evaluations demonstrate that WDM-UNet consistently outperforms state-of-the-art methods, achieving 96.92% accuracy, 83.61% sensitivity, and an 82.87% F1-score in the DRIVE dataset, with superior performance across all the benchmark datasets in both segmentation accuracy and robustness, particularly in complex vascular scenarios. Full article
(This article belongs to the Section Sensing and Imaging)
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15 pages, 611 KiB  
Review
Role of Dyadic Proteins in Proper Heart Function and Disease
by Carter Liou and Michael T. Chin
Int. J. Mol. Sci. 2025, 26(15), 7478; https://doi.org/10.3390/ijms26157478 - 2 Aug 2025
Viewed by 199
Abstract
Cardiovascular disease encompasses a wide group of conditions that affect the heart and blood vessels. Of these diseases, cardiomyopathies and arrhythmias specifically have been well-studied in their relationship to cardiac dyads, nanoscopic structures that connect electrical signals to muscle contraction. The proper development [...] Read more.
Cardiovascular disease encompasses a wide group of conditions that affect the heart and blood vessels. Of these diseases, cardiomyopathies and arrhythmias specifically have been well-studied in their relationship to cardiac dyads, nanoscopic structures that connect electrical signals to muscle contraction. The proper development and positioning of dyads is essential in excitation–contraction (EC) coupling and, thus, beating of the heart. Three proteins, namely CMYA5, JPH2, and BIN1, are responsible for maintaining the dyadic cleft between the T-tubule and junctional sarcoplasmic reticulum (jSR). Various other dyadic proteins play integral roles in the primary function of the dyad—translating a propagating action potential (AP) into a myocardial contraction. Ca2+, a secondary messenger in this process, acts as an allosteric activator of the sarcomere, and its cytoplasmic concentration is regulated by the dyad. Loss-of-function mutations have been shown to result in cardiomyopathies and arrhythmias. Adeno-associated virus (AAV) gene therapy with dyad components can rescue dyadic dysfunction, which results in cardiomyopathies and arrhythmias. Overall, the dyad and its components serve as essential mediators of calcium homeostasis and excitation–contraction coupling in the mammalian heart and, when dysfunctional, result in significant cardiac dysfunction, arrhythmias, morbidity, and mortality. Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Histopathological and Molecular Diagnostics)
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23 pages, 1585 KiB  
Article
The Key Role of Thermal Relaxation Time on the Improved Generalized Bioheat Equation: Analytical Versus Simulated Numerical Approach
by Alexandra Maria Isabel Trefilov, Mihai Oane and Liviu Duta
Materials 2025, 18(15), 3524; https://doi.org/10.3390/ma18153524 - 27 Jul 2025
Viewed by 366
Abstract
The Pennes bioheat equation is the most widely used model for describing heat transfer in living tissue during thermal exposure. It is derived from the classical Fourier law of heat conduction and assumes energy exchange between blood vessels and surrounding tissues. The literature [...] Read more.
The Pennes bioheat equation is the most widely used model for describing heat transfer in living tissue during thermal exposure. It is derived from the classical Fourier law of heat conduction and assumes energy exchange between blood vessels and surrounding tissues. The literature presents various numerical methods for solving the bioheat equation, with exact solutions developed for different boundary conditions and geometries. However, analytical models based on this framework are rarely reported. This study aims to develop an analytical three-dimensional model using MATHEMATICA software, with subsequent mathematical validation performed through COMSOL simulations, to characterize heat transfer in biological tissues induced by laser irradiation under various therapeutic conditions. The objective is to refine the conventional bioheat equation by introducing three key improvements: (a) incorporating a non-Fourier framework for the Pennes equation, thereby accounting for the relaxation time in thermal response; (b) integrating Dirac functions and the telegraph equation into the bioheat model to simulate localized point heating of diseased tissue; and (c) deriving a closed-form analytical solution for the Pennes equation in both its classical (Fourier-based) and improved (non-Fourier-based) formulations. This paper investigates the nuanced relationship between the relaxation time parameter in the telegraph equation and the thermal relaxation time employed in the bioheat transfer equation. Considering all these aspects, the optimal thermal relaxation time determined for these simulations was 1.16 s, while the investigated thermal exposure time ranged from 0.01 s to 120 s. This study introduces a generalized version of the model, providing a more realistic representation of heat exchange between biological tissue and blood flow by accounting for non-uniform temperature distribution. It is important to note that a reasonable agreement was observed between the two modeling approaches: analytical (MATHEMATICA) and numerical (COMSOL) simulations. As a result, this research paves the way for advancements in laser-based medical treatments and thermal therapies, ultimately contributing to more optimized therapeutic outcomes. Full article
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14 pages, 954 KiB  
Article
Left Ventricular Ejection Fraction Predicts Outcomes in Different Subgroups of Patients Undergoing Coronary Angiography
by Henning Johann Steffen, Tobias Schupp, Mohammad Abumayyaleh, Lasse Kuhn, Philipp Steinke, Jonas Dudda, Kathrin Weidner, Jonas Rusnak, Mahboubeh Jannesari, Fabian Siegel, Daniel Duerschmied, Michael Behnes and Ibrahim Akin
J. Clin. Med. 2025, 14(15), 5219; https://doi.org/10.3390/jcm14155219 - 23 Jul 2025
Viewed by 299
Abstract
Objectives: To evaluate the long-term prognostic value of left ventricular ejection fraction (LVEF) in consecutive patients undergoing invasive coronary angiography (CA). Background: LVEF is a key prognostic marker in cardiovascular disease, but its value across different clinical indications for CA remains insufficiently characterized. [...] Read more.
Objectives: To evaluate the long-term prognostic value of left ventricular ejection fraction (LVEF) in consecutive patients undergoing invasive coronary angiography (CA). Background: LVEF is a key prognostic marker in cardiovascular disease, but its value across different clinical indications for CA remains insufficiently characterized. Methods: Consecutive patients undergoing CA between January 2016 and August 2022 were retrospectively included at one institution. Patients were stratified into four LVEF groups: ≥ 55%, 45–54%, 35–44%, and <35%. The primary endpoint was rehospitalization for heart failure (HF) at 36 months. Secondary endpoints were acute myocardial infarction (AMI) and coronary revascularization. Kaplan–Meier and multivariable Cox regression analyses were conducted within the entire study cohort and pre-defined subgroups. Results: A total of 6888 patients were included (median age: 71 years; 65.2% males). LVEF < 35% was associated with a higher comorbidity burden and more extensive coronary artery disease (e.g., three-vessel CAD: 38.6% vs. 20.7%, p < 0.001). Event rates for HF rehospitalization and AMI increased progressively with declining LVEF, while revascularization rates varied across categories. Statistically significant differences across LVEF groups were observed for all three endpoints in unadjusted analyses (log-rank p < 0.001). In multivariable models, LVEF < 35% independently predicted HF rehospitalization (HR = 3.731, p < 0.001) and AMI (HR = 4.184, p < 0.001), but not revascularization (HR = 0.867, p = 0.378). The prognostic association was demonstrated across all subgroups stratified by age, sex, subtype of acute coronary syndrome, and CAD severity. Conclusions: Reduced LVEF is an independent predictor of HF rehospitalization and AMI in patients undergoing coronary angiography, irrespective of its indication, whereas no independent association was observed with coronary revascularization. Full article
(This article belongs to the Section Cardiology)
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18 pages, 2500 KiB  
Article
Hyperthermia Augments the H1-Histamine Receptor-Mediated Force in the Human Atrium
by Thanh Hoai Pham, Peter Grundig, Britt Hofmann, Uwe Kirchhefer, Joachim Neumann and Ulrich Gergs
Int. J. Mol. Sci. 2025, 26(14), 6842; https://doi.org/10.3390/ijms26146842 - 16 Jul 2025
Viewed by 201
Abstract
It was unknown whether hyperthermia increased the efficacy of histamine to raise the force of cardiac contractions via human H1-histamine receptors. To that end, we measured the force in isolated human atrial preparations (HAPs) excised from the right atrium of patients who underwent [...] Read more.
It was unknown whether hyperthermia increased the efficacy of histamine to raise the force of cardiac contractions via human H1-histamine receptors. To that end, we measured the force in isolated human atrial preparations (HAPs) excised from the right atrium of patients who underwent cardiac surgery due to severe two- or three-vessel coronary heart disease. For comparison, we also measured the force in paced (1 Hz) left and spontaneously beating right atrial preparations of transgenic mice overexpressing cardiac human H1-histamine receptors (H1-TG). Histamine (100 µM) was less efficient in raising the force in left atrial preparations from H1 TG mouse atria under hyperthermia than under hypothermia. Oppositely, histamine was more efficient in augmenting force during hyperthermia than during hypothermia in isolated electrically stimulated (1 Hz) HAPs. In sum, the contractile response to activation of H1-histamine receptor in H1-TG mice and in HAPs are opposite with regard to hyperthermia dependence. In patients with fever, histamine might thus be important, to preserve cardiac contractile function as a compensatory mechanism. Full article
(This article belongs to the Section Molecular Pharmacology)
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12 pages, 2335 KiB  
Article
Ultrawide-Field Optical Coherence Tomography Angiography-Guided Navigated Laser Therapy of Non-Perfused Areas in Branch Retinal Vein Occlusion
by Yao Zhou, Peng Peng, Jiaojiao Wei, Jian Yu and Min Wang
J. Clin. Med. 2025, 14(14), 5014; https://doi.org/10.3390/jcm14145014 - 15 Jul 2025
Viewed by 245
Abstract
Background/Objectives: This study evaluates whether ultrawide-field optical coherence tomography angiography (UWF-OCTA) can guide navigated laser therapy for non-perfused areas (NPAs) in branch retinal vein occlusion (BRVO). It further explores whether the laser spots can be accurately placed according to plan, considering that [...] Read more.
Background/Objectives: This study evaluates whether ultrawide-field optical coherence tomography angiography (UWF-OCTA) can guide navigated laser therapy for non-perfused areas (NPAs) in branch retinal vein occlusion (BRVO). It further explores whether the laser spots can be accurately placed according to plan, considering that the retina is three-dimensional (3D), while UWF-OCTA provides two-dimensional (2D) images. Methods: UWF-OCTA images from three devices—VG200, Xephilio OCT-S1, and Bmizar—guided the treatments. These images were superimposed onto NAVILAS® system images to guide NPA treatments. Pre-treatment planning was strategically designed to avoid normal and collateral vessels, with immediate post-laser OCTA and en face images assessing the efficacy of the laser spots in avoiding these vessels as planned. The accuracy of navigated laser therapy was further analyzed by comparing the intended laser locations with the actual spots. Results: All montaged OCTA images from the three devices were seamlessly integrated into the navigated laser system without registration errors. All patients received treatments targeting the NPAs as planned. However, not all collateral or normal vessels were successfully avoided by the laser spots. A further analysis revealed that the actual locations of the laser spots deviated slightly from the planned locations, particularly in the mid-periphery areas. Conclusions: UWF-OCTA-guided navigated laser photocoagulation is feasible and precise for treating NPAs in BRVO. Nonetheless, minor deviations between planned and actual locations were observed. This discrepancy, particularly important when treating diseases of the macular area, should be carefully considered when employing OCTA-guided navigated laser photocoagulation. Full article
(This article belongs to the Section Ophthalmology)
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16 pages, 10545 KiB  
Article
Macular Microvasculature Is Different in Patients with Primary Sjögren’s Disease Compared to Healthy Controls
by Gyde Tadsen, Nadine Zehrfeld, Laura Hoffmann, Marten Gehlhaar, Bettina Hohberger, Christian Mardin, Torsten Witte, Carsten Framme, Diana Ernst and Katerina Hufendiek
Diagnostics 2025, 15(13), 1701; https://doi.org/10.3390/diagnostics15131701 - 3 Jul 2025
Viewed by 351
Abstract
Background/Objectives: This study investigates the macular microvasculature in a large cohort of primary Sjögren’s disease (SjD) patients using optical coherence tomography angiography (OCTA), focusing on how disease duration, activity, and hydroxychloroquine (HCQ) treatment influence retinal microcirculation. Methods: A total of 106 eyes [...] Read more.
Background/Objectives: This study investigates the macular microvasculature in a large cohort of primary Sjögren’s disease (SjD) patients using optical coherence tomography angiography (OCTA), focusing on how disease duration, activity, and hydroxychloroquine (HCQ) treatment influence retinal microcirculation. Methods: A total of 106 eyes (53 SjD patients) and 70 eyes (35 age- and gender-matched healthy controls (HCs)) were examined. The vessel area density (VAD, %) and foveal avascular zone (FAZ, mm2) were measured in three retinal layers: Superficial Vascular Plexus (SVP), Intermediate Capillary Plexus (ICP), and Deep Capillary Plexus (DCP), respectively, in three peri-macular circular sectors (c1, c2, c3) each. Results: The VAD was significantly lower in c1 of the DCP in SjD compared to HCs (29.14 ± 7.07 vs. 31.78 ± 9.55, p = 0.038). The FAZ was significantly larger in SjD in both SVP (0.41 ± 0.13 vs. 0.34, 0.11, p < 0.001; Cohen’s |d| = 0.55) and DCP (0.45 ± 0.15 vs. 0.4 ± 0.14, p = 0.014; Cohen’s |d| ± 0.38). Significant correlations were observed between the FAZ size and reductions in the VAD in the SVP and DCP (p = 0.010, Cohen’s |d| = 0.2; p < 0.001, Cohen’s |d| ± 0.26) and across all layers combined (p = 0.019, Cohen’s |d| = −0.18). Conclusions: There was a negative correlation between the VAD in the DCP and disease duration (ρ = −0.28, p = 0.040). No significant correlation was identified between the duration of HCQ intake and the VAD or FAZ. Our findings indicate microvascular alterations in the DCP of SjD, characterized by a reduced VAD and an enlarged FAZ, which may be attributable to inflammatory or arteriosclerotic factors. OCTA may prove to be a valuable tool for the stratification of vascular risk in SjD. Full article
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16 pages, 6657 KiB  
Article
Experimental Assessment of YOLO Variants for Coronary Artery Disease Segmentation from Angiograms
by Eduardo Díaz-Gaxiola, Arturo Yee-Rendon, Ines F. Vega-Lopez, Juan Augusto Campos-Leal, Iván García-Aguilar, Ezequiel López-Rubio and Rafael M. Luque-Baena
Electronics 2025, 14(13), 2683; https://doi.org/10.3390/electronics14132683 - 2 Jul 2025
Viewed by 529
Abstract
Coronary artery disease (CAD) is one of the leading causes of mortality worldwide, highlighting the importance of developing accurate and efficient diagnostic tools. This study presents a comparative evaluation of three recent YOLO architecture versions (YOLOv8, YOLOv9, and YOLOv11) for the tasks of [...] Read more.
Coronary artery disease (CAD) is one of the leading causes of mortality worldwide, highlighting the importance of developing accurate and efficient diagnostic tools. This study presents a comparative evaluation of three recent YOLO architecture versions (YOLOv8, YOLOv9, and YOLOv11) for the tasks of coronary vessel segmentation and stenosis detection using the ARCADE dataset. Two workflows were explored: one with original angiographic images and another incorporating Contrast Limited Adaptive Histogram Equalization (CLAHE) for image enhancement. Models were trained for 100 epochs using the AdamW optimizer and evaluated with precision, recall, and F1-score under a pixel-based segmentation framework. YOLOv9-E achieved the highest performance in vessel segmentation with an F1-score of 0.4524, while YOLOv11-X was most effective for stenosis detection, achieving an F1-score of 0.7826. Although CLAHE improved local contrast, it did not consistently improve segmentation results and occasionally introduced artifacts that negatively affected model performance. Compared to state-of-the-art methods, the YOLO models demonstrated competitive results, especially for large, well-defined coronary segments, but showed limitations in detecting smaller or more complex pathological structures. These findings support the use of YOLO-based architectures for real-time CAD segmentation tasks and highlight opportunities for future improvement through the integration of attention mechanisms or hybrid deep learning strategies. Full article
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12 pages, 1120 KiB  
Case Report
First Case of Infective Endocarditis Caused by Vibrio metschnikovii: Clinico-Diagnostic Complexities and a Systematic Literature Review
by Alessandro Carrozzo, Vittorio Bolcato, Luigi Martinelli, Ferdinando Dodi, Antonella Vulcano, Giuseppe Basile and Livio P. Tronconi
Clin. Pract. 2025, 15(7), 118; https://doi.org/10.3390/clinpract15070118 - 25 Jun 2025
Viewed by 422
Abstract
Background: Non-cholera Vibrio species are rare waterborne pathogens that can cause severe infections. Among these, few cases of Vibrio metschnikovii infections have been reported, especially in the gastrointestinal tract, with no cardiac tissue involvement as a result. Following the PRISMA checklist, we conducted [...] Read more.
Background: Non-cholera Vibrio species are rare waterborne pathogens that can cause severe infections. Among these, few cases of Vibrio metschnikovii infections have been reported, especially in the gastrointestinal tract, with no cardiac tissue involvement as a result. Following the PRISMA checklist, we conducted a literature review, and thirteen articles for twenty-two cases overall were included: seven cases of sepsis (in three cases, the echocardiographic results were negative), seven cases of pneumonia, two skin infections, eleven cases of diarrhoea, and a gastroenteritis outbreak. This report documents the expanding clinical spectrum and the role played by V. metschnikovii in infective endocarditis. Case report: A 28-year-old male patient was referred to the cardiac surgery unit for urgent mitral valve replacement due to suspicion of infective endocarditis. Microbiological tests yielded negative results. Following recovery and discharge with antimicrobial therapy for 6 weeks, the patient experienced prosthesis detachment, necessitating re-hospitalisation for an emergency valve replacement. Vibrio metschnikovii was identified on the prosthesis valve through PCR and successfully treated with ciprofloxacin. However, a spontaneous rupture of the ascending thoracic aorta led to a neurological injury. Discussion: This case represents the first case of valve infection caused by Vibrio metschnikovii, characterised by diagnostic and therapeutic challenges and the involvement of the great vessels. Also considered in this case, for a disease with a median age of 58 years (11–83) and a male-to-female ratio of 2.2, were one male neonate and six cases for whom neither sex nor age was indicated. Excluding gastrointestinal cases, the septic forms are associated with high morbidity, although the single case described involved a young and healthy subject. Risk factors for the pathogen or predisposing/pathological conditions for endocarditis did not emerge. The routes and the time of infection could not be determined, deepening the possibility of occupational exposure via the patient’s position as a boat worker. Poor sensitivity to third-generation cephalosporins has been reported in the literature: the absence of an antibiogram does not allow for a comparison, although resolution was achieved with ciprofloxacin. Conclusion: The rising global incidence of non-cholera Vibrio infections, driven by environmental changes, calls for urgent research into the factors behind their pathogenicity and infection routes. Diagnostic complexities have emerged together with clinical severity. Full article
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19 pages, 506 KiB  
Review
Immunopathology of Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis
by Katarzyna Aleksandra Lisowska and Anna Wardowska
Int. J. Mol. Sci. 2025, 26(13), 6065; https://doi.org/10.3390/ijms26136065 - 24 Jun 2025
Viewed by 632
Abstract
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes a group of rare diseases characterized by autoimmune-associated inflammation and vessel damage. Based on the clinical manifestations and involvement of immune components, three disease syndromes are distinguished: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic [...] Read more.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes a group of rare diseases characterized by autoimmune-associated inflammation and vessel damage. Based on the clinical manifestations and involvement of immune components, three disease syndromes are distinguished: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). In this review, we present the current data on the epidemiology, the clinical manifestations of each syndrome, and the most up-to-date classification criteria. The role of the underlying genetic and epigenetic abnormalities, as well as their interplay, is described. The immunological diversification of AAV is also described, with a focus on the immune cell dysfunctions detected in patients. In conclusion, we emphasize the urgent need to unravel the sophisticated mechanisms of this disease, which would enable the development of new, effective therapeutic strategies. Full article
(This article belongs to the Special Issue The Molecular Basis of Vascular Pathology)
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11 pages, 4039 KiB  
Case Report
Structural, Functional, and Cellular Analysis of a Case of Acute Zonal Occult Outer Retinopathy (AZOOR)
by Mattia Iuliano, Marco Lombardo, Benedetto Falsini, Jacopo Sebastiani, Michele D’Ambrosio, Francesco Martelli and Andrea Cusumano
Biomedicines 2025, 13(7), 1521; https://doi.org/10.3390/biomedicines13071521 - 21 Jun 2025
Viewed by 496
Abstract
Background: Adaptive optics transscleral flood illumination (AO-TFI) enables in vivo, non-invasive, high-resolution imaging of retinal pigment epithelium (RPE) and photoreceptor (PR) cells, paving the way for a new potential characterization of retinal diseases. This study aimed to analyze RPE and PR cells in [...] Read more.
Background: Adaptive optics transscleral flood illumination (AO-TFI) enables in vivo, non-invasive, high-resolution imaging of retinal pigment epithelium (RPE) and photoreceptor (PR) cells, paving the way for a new potential characterization of retinal diseases. This study aimed to analyze RPE and PR cells in a case of acute zonal occult outer retinopathy (AZOOR) using AO-TFI. Methods: A patient affected by AZOOR underwent a comprehensive eye examination, perimetry, electroretinography (ERG), autofluorescence, and optical coherence tomography (OCT) during the acute phase (T0). After three years (T1), OCT angiography (OCTA) and AO-TFI were also performed. Voronoi analysis was utilized to quantify RPE and PR cells. Results: At T0, OCT revealed interruptions in the ellipsoid zone (EZ) of the right eye, while the structure of the left eye appeared normal. Perimetry and ERG were abnormal in both eyes. At T1, OCT indicated recovery of the EZ in the right eye, while thinning of the ONL persisted. Perimetry and mfERG values remained below normative limits. OCTA exhibited globally reduced vessel density in the inner retina of the right eye. AO-TFI demonstrated reduced PR density in affected areas despite preserved EZ, while RPE cell density appeared unaffected. Conclusion: AO-TFI enabled a detailed visualization and quantification of macular RPE and PR cells, providing valuable insights into the pathophysiology of AZOOR. Full article
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28 pages, 13615 KiB  
Article
The Anti-Parkinsonian A2A Receptor Antagonist Istradefylline (KW-6002) Attenuates Behavioral Abnormalities, Neuroinflammation, and Neurodegeneration in Cerebral Ischemia: An Adenosinergic Signaling Link Between Stroke and Parkinson’s Disease
by Michael G. Zaki, Elisabet Jakova, Mahboubeh Pordeli, Elina Setork, Changiz Taghibiglou and Francisco S. Cayabyab
Int. J. Mol. Sci. 2025, 26(12), 5680; https://doi.org/10.3390/ijms26125680 - 13 Jun 2025
Viewed by 1424
Abstract
Stroke, the third leading cause of death worldwide, is a major cause of functional disability. Cerebral ischemia causes a rapid elevation of adenosine, the main neuromodulator in the brain. The inhibition of adenosine A2A receptors (A2ARs) has been introduced as a potential target [...] Read more.
Stroke, the third leading cause of death worldwide, is a major cause of functional disability. Cerebral ischemia causes a rapid elevation of adenosine, the main neuromodulator in the brain. The inhibition of adenosine A2A receptors (A2ARs) has been introduced as a potential target in neurodegenerative disorders involving extracellular adenosine elevation. Istradefylline, a selective A2AR antagonist, has been approved for Parkinson’s disease (PD) adjunctive therapy and showed neuroprotective effects in PD and Alzheimer’s disease. However, the role of A2ARs in post-stroke neuronal damage and behavioral deficits remains unclear. We recently showed that A2AR antagonism prevented the adenosine-induced post-hypoxia synaptic potentiation of glutamatergic neurotransmission following the hypoxia/reperfusion of hippocampal slices. Here, we investigated the potential neuroprotective effects of istradefylline in male Sprague-Dawley rats subjected to pial vessel disruption (PVD) used to model a small-vessel stroke. Rats were treated with either a vehicle control or istradefylline (3 mg/kg i.p.) following PVD surgery for three days. Istradefylline administration prevented anxiety and depressive-like behaviors caused by PVD stroke. In addition, istradefylline significantly attenuated ischemia-induced cognitive impairment and motor deficits. Moreover, istradefylline markedly reduced hippocampal neurodegeneration, as well as GFAP/Iba-1, TNF-α, nNOS, and iNOS levels after PVD, but prevented the downregulation of anti-inflammatory markers TGF-β1 and IL-4. Together, these results suggest a molecular link between stroke and PD and that the anti-PD drug istradefylline displays translational potential for drug repurposing as a neuroprotective agent for cerebral ischemic damage. Full article
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13 pages, 410 KiB  
Review
Steal Syndrome in Free Flap Microvascular Reconstruction of the Lower Extremity: Systematic Review of Incidence, Risk Factors, and Surgical Management
by Georgios Karamitros, Ilias Iliadis, Raymond A. Pensy and Gregory A. Lamaris
Bioengineering 2025, 12(6), 647; https://doi.org/10.3390/bioengineering12060647 - 12 Jun 2025
Viewed by 539
Abstract
Background: Steal syndrome in the setting of microvascular reconstruction refers to a phenomenon whereby blood flow is diverted from the native tissue to the free flap, leading to ischemia and potential limb loss. In the present study, we aim to comprehensively evaluate [...] Read more.
Background: Steal syndrome in the setting of microvascular reconstruction refers to a phenomenon whereby blood flow is diverted from the native tissue to the free flap, leading to ischemia and potential limb loss. In the present study, we aim to comprehensively evaluate the occurrence and management of steal syndrome in free flap reconstruction of the lower extremities. Methods: A thorough literature search was conducted across the MEDLINE, Embase, Cochrane Library, and Scopus databases up to 29 January 2025. Studies were selected based on predefined inclusion criteria focusing on free flap microvascular reconstruction in the lower extremities with a focus on steal syndrome. Two independent reviewers assessed and extracted data. Results: Three studies were included, involving seven patients, with a mean age of 65.66 ± 5.89 years, who developed steal syndrome following free flap microvascular reconstruction. The most common revision involved below-the-knee amputation (BKA) due to ischemic complications. Comorbidities such as peripheral vascular disease (PVD), diabetes, and hypertension were present in all cases. The majority of anastomoses (85.7%) were end-to-side (ETS), with only one case utilizing a flow-through configuration. The majority of cases (n = 5, 71.4%) were reconstructed using latissimus dorsi (LD) flaps, with the remaining two cases using rectus abdominis (n = 1) and gracilis (n = 1) flaps. The recipient vessel was the anterior tibial artery in two patients (28.6%), the dorsalis pedis artery in two patients (28.6%), and the popliteal artery in three patients (42.9%). The most common salvage procedure was below-the-knee amputation (BKA), performed in four patients (57.1%). One patient required revision of the venous anastomosis and flap debridement, followed by a Chopart amputation (n = 1, 14.3%). Conclusions: The occurrence of steal syndrome in free flap microvascular reconstruction of the lower extremities is rare but can lead to significant complications, including amputation. The findings indicate that steal syndrome is more likely in patients with pre-existing vascular conditions such as PVD and diabetes. While surgical technique and flap type may influence its development, further studies are needed to identify specific anatomical and clinical predictors. The absence of a unified treatment guideline underscores the need for further investigation into effective management strategies to prevent amputation and optimize patient outcomes. Full article
(This article belongs to the Special Issue Surgical Wound Infections and Management)
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Article
Prolonged In Vivo Chemogenetic Generation of Hydrogen Peroxide by Endothelial Cells Induces Cardiac Remodelling and Vascular Dysfunction
by Melina Lopez, Niklas Herrle, Bardia Amirmiran, Pedro F. Malacarne, Julia Werkhäuser, Souradeep Chatterjee, Carine Kader, Victoria Jurisch, Xin Wen, Maedeh Gheisari, Katrin Schäfer, Christian Münch, Florian Leuschner, Ralf Gilsbach, Flávia Rezende and Ralf P. Brandes
Antioxidants 2025, 14(6), 705; https://doi.org/10.3390/antiox14060705 - 10 Jun 2025
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Abstract
Increased levels of reactive oxygen species (ROS) are a hallmark of cardiovascular disease. ROS impact the function of proteins largely through thiol modification leading to redox signalling. Acute, targeted interference with local ROS levels has been difficult. Therefore, how dynamics in redox signalling [...] Read more.
Increased levels of reactive oxygen species (ROS) are a hallmark of cardiovascular disease. ROS impact the function of proteins largely through thiol modification leading to redox signalling. Acute, targeted interference with local ROS levels has been difficult. Therefore, how dynamics in redox signalling impact cardiovascular health is still a matter of current research. An inducible, endothelial cell-specific knock-in mouse model expressing a yeast D-amino acid oxidase enzyme was generated (Hipp11-Flox-Stop-Flox-yDAO-Cdh5-CreERT2+/0 referred to as ecDAO). DAO releases H2O2 as a by-product of the conversion of D-amino acids into imino acids. The D-amino acid treatment of DAO-expressing cells therefore increases their intracellular H2O2 production. The induction of yDAO in the ecDAO mice was performed with tamoxifen. Subsequently, the mice received D-Alanine (D-Ala, 0.5 M) through drinking water, and the effects on ROS production and vascular and cardiac function were determined. ecDAO induction increased endothelial ROS production as well as ROS production in the lung, which is rich in endothelial cells. The functional consequences of this were, however limited: After minimally invasive myocardial infarction, there was no difference in the outcome between the control (CTL) and ecDAO mice. With respect to vascular function, three days of D-Ala slightly improved vascular function as demonstrated by an increase in the diameter of the carotid artery in vivo and decreased vessel constriction to phenylephrine. Fifty-two days of D-Ala induced cardiac remodelling, increased peripheral resistance, and overoxidation of peroxiredoxins. In conclusion, acute stimulation of endothelial ROS improves cardiovascular function, whereas prolonged ROS exposure deteriorates it. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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