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18 pages, 2630 KiB  
Article
Multimodal Imaging of Diabetic Retinopathy: Insights from Optical Coherence Tomography Angiography and Adaptive Optics
by Andrada-Elena Mirescu, Dan George Deleanu, Sanda Jurja, Alina Popa-Cherecheanu, Florian Balta, Gerhard Garhofer, George Balta, Irina-Elena Cristescu and Ioana Teodora Tofolean
Diagnostics 2025, 15(14), 1732; https://doi.org/10.3390/diagnostics15141732 - 8 Jul 2025
Viewed by 335
Abstract
Background/Objectives: To investigate the role of multimodal imaging, specifically optical coherence tomography angiography (OCTA) and adaptive optics (AO), in the diagnosis and monitoring of diabetic retinopathy. Methods: Our study represents an observational, cross-sectional analysis including sixty-nine patients from four distinct groups: [...] Read more.
Background/Objectives: To investigate the role of multimodal imaging, specifically optical coherence tomography angiography (OCTA) and adaptive optics (AO), in the diagnosis and monitoring of diabetic retinopathy. Methods: Our study represents an observational, cross-sectional analysis including sixty-nine patients from four distinct groups: a control group (17 patients), diabetic patients without diabetic retinopathy (no DR) (14 patients), diabetic patients with non-proliferative diabetic retinopathy (NPDR) (18 patients), and diabetic patients with proliferative diabetic retinopathy (PDR patients). A comprehensive ophthalmological evaluation, along with high-resolution imaging using OCTA and AO, was performed. OCTA images of the superficial capillary plexus, acquired with the OCT Angio Topcon, were analyzed using a custom-developed MATLAB algorithm, while AO retinal vascular images were evaluated with the manufacturer’s software of the Adaptive Optics Retinal Camera rtx1™. Results: Our findings demonstrated statistically significant reductions in foveal avascular zone circularity, superficial capillary plexus density, vessel length density, and fractal dimension, correlating with the severity of diabetic retinopathy, particularly in the PDR. Additionally, mean wall thickness and wall-to-lumen ratio were significantly increased in patients with diabetic retinopathy, notably in PDR. Conclusions: In conclusion, our findings demonstrate that the combined use of OCTA and AO imaging offers complementary insights into the microvascular alterations associated with diabetic retinopathy progression and severity. These high-resolution modalities together reveal both perfusion deficits and structural vascular changes, underscoring their utility as essential tools for early detection, staging, monitoring, and informed management of DR. Full article
(This article belongs to the Special Issue OCT and OCTA Assessment of Retinal and Choroidal Diseases)
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9 pages, 3832 KiB  
Case Report
Non-Invasive Diagnostic Imaging in Kaposi Sarcoma Evaluation
by Carmen Cantisani, Antonio Di Guardo, Marco Ardigò, Mariano Suppa, Salvador Gonzalez, Caterina Longo, Alberto Taliano, Emanuele Rovaldi, Elisa Cinotti and Giovanni Pellacani
Diagnostics 2025, 15(13), 1665; https://doi.org/10.3390/diagnostics15131665 - 30 Jun 2025
Viewed by 323
Abstract
Background and Clinical Significance: Kaposi sarcoma (KS) is a rare angio-proliferative mesenchymal tumor that predominantly affects the skin and mucous membranes but may involve lymph nodes and visceral organs. Clinically, it manifests as red-purple-brown papules, nodules, or plaques, either painless or painful, often [...] Read more.
Background and Clinical Significance: Kaposi sarcoma (KS) is a rare angio-proliferative mesenchymal tumor that predominantly affects the skin and mucous membranes but may involve lymph nodes and visceral organs. Clinically, it manifests as red-purple-brown papules, nodules, or plaques, either painless or painful, often with disfiguring potential. The diagnosis is traditionally based on clinical and histopathological evaluation, although non-invasive imaging techniques are increasingly used to support diagnosis and treatment monitoring. We report a case of HHV-8-negative Kaposi sarcoma evaluated with multiple non-invasive imaging modalities to highlight their diagnostic utility. Case Presentation: An 83-year-old man presented with multiple painful, violaceous papulo-nodular lesions, some ulcerated, on the lateral aspect of his left foot. Dermoscopy revealed the characteristic rainbow pattern. Dynamic Optical Coherence Tomography (D-OCT) allowed real-time visualization of microvascular abnormalities, identifying large serpentine and branching vessels with clearly delineated capsules. Line-field Optical Coherence Tomography (LC-OCT) showed irregular dermal collagen, vascular lacunae, and the presence of spindle cells and slit-like vessels. Histological analysis confirmed the diagnosis of Kaposi sarcoma, revealing a proliferation of spindle-shaped endothelial cells forming angulated vascular spaces, with red blood cell extravasation and a mixed inflammatory infiltrate. Conclusions: Non-invasive imaging tools, including dermoscopy, D-OCT, and LC-OCT, have emerged as valuable adjuncts in the diagnosis and monitoring of KS. These techniques enable in vivo assessment of vascular architecture and tissue morphology, enhancing clinical decision-making while reducing the need for immediate biopsy. Dermoscopy reveals polychromatic vascular features, such as the rainbow pattern, while D-OCT and LC-OCT provide high-resolution insights into vascular proliferation, tissue heterogeneity, and cellular morphology. Dermoscopy, dynamic OCT, and LC-OCT represent promising non-invasive diagnostic tools for the assessment of Kaposi sarcoma. These technologies provide detailed morphological and vascular information, enabling earlier diagnosis and more personalized management. While histopathology remains the gold standard, non-invasive imaging offers a valuable complementary approach for diagnosis and follow-up, particularly in complex or atypical presentations. Ongoing research and technological refinement are essential to improve accessibility and clinical applicability. Full article
(This article belongs to the Special Issue Optical Coherence Tomography in Non-Invasive Diagnostic Imaging)
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10 pages, 944 KiB  
Article
Morphometric Measurements Prior to Totally Endoscopic Mitral Valve Repair: Technical and Educational Aspects
by Marie-Elisabeth Stelzmueller, Daniel Zimpfer and Wilfried Wisser
J. Clin. Med. 2025, 14(8), 2581; https://doi.org/10.3390/jcm14082581 - 9 Apr 2025
Viewed by 485
Abstract
Objective: The totally endoscopic approach is on the rise to become the new standard in mitral valve surgery. The aim of this study was to develop a morphometric measurement tool for educational purposes to predict operability with low conversion and high repair [...] Read more.
Objective: The totally endoscopic approach is on the rise to become the new standard in mitral valve surgery. The aim of this study was to develop a morphometric measurement tool for educational purposes to predict operability with low conversion and high repair rates. Methods: From January 2020 to March 2023, 64 patients underwent totally endoscopic mitral valve repair (TE-MVR). Of these, 15 patients were deemed to be unsuitable for TE-MVR due to narrow space and/or anticipated complex repair techniques and underwent repair through sternotomy (MVR-open). Angio-CT scanning was performed for preoperative planning and measurements of the following: the distance between the sternum and the spine (DSS), the distance between the skin incision and the anterior anulus of the mitral valve (DNM) and the intercostal space at the level of the skin incision (ICS). Results: The repair rate for all patients was 98.7%. In the TE-MVR group, the conversion rate to sternotomy was 3.1%. The 30-day survival was 100%. The DSS was 130.4 ± 18.8 mm and 108.1 ± 17.3 mm, and the DSM 70.7 ± 12.1 mm and 58.5 ± 13.6 mm in the TE-MVR and MVR-open, respectively (p < 0.001). Twenty-one TE-MVR patients were found to be technically demanding due to friction and less freedom to move the instruments. The composite morphometric parameter DSS plus 4xICS minus DNM was 53.3, 39.8 and 25.6 for TE-TMReasy, TE-TMRdemanding and MVR-open, respectively (p < 0.05 and p < 0.01). Conclusions: Surgical skills and a long history of expertise are mandatory to achieve excellent results with a low conversion and high repair rate. The composite morphometric parameter may be an easy tool for educational demands to predict the ease and feasibility of TE-MVR. Full article
(This article belongs to the Special Issue Mitral Valve Surgery: Current Status and Future Challenges)
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14 pages, 565 KiB  
Article
Assessment of OCT and Angio-OCT Parameters in Keratoconus Patients with and without Penetrating Keratoplasty
by Anna Maria Gadamer, Piotr Miklaszewski, Dominika Janiszewska-Bil, Anita Lyssek-Boroń, Dariusz Dobrowolski, Edward Wylęgała, Beniamin Oskar Grabarek, Aleksandra Kiełbasińska and Katarzyna Krysik
J. Clin. Med. 2024, 13(17), 5111; https://doi.org/10.3390/jcm13175111 - 28 Aug 2024
Cited by 1 | Viewed by 1452
Abstract
Background/Objectives: Keratoconus (KC) is a bilateral eye disease characterized by corneal thinning and cone-like deformation, leading to visual impairment. This study evaluated the radial peripapillary capillaries (RPCs) in keratoconus patients with and without penetrating keratoplasty (PKP) using OCT and angio-OCT, comparing the results [...] Read more.
Background/Objectives: Keratoconus (KC) is a bilateral eye disease characterized by corneal thinning and cone-like deformation, leading to visual impairment. This study evaluated the radial peripapillary capillaries (RPCs) in keratoconus patients with and without penetrating keratoplasty (PKP) using OCT and angio-OCT, comparing the results to a control group. Methods: This retrospective study included 149 eyes, 97 from patients who underwent PKP between January 2018 and February 2023 and 52 from patients who did not undergo PKP. The control group comprised 72 patients (144 eyes) who were healthy volunteers. Measurements included the best corrected visual acuity (BCVA), the intraocular pressure (IOP), slit-lamp biomicroscopy, a fundus examination, and corneal topography, as well as OCT and angio-OCT assessments of the RPCs, retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), and central retinal thickness (CRT). Statistical analyses were performed using Student’s t-test and Pearson’s correlation coefficient. Results: The RNFL was significantly thinner in KC eyes after PKP compared to control eyes (p < 0.001), and the CRT was significantly thicker in KC eyes after PKP compared to control eyes (p = 0.003). However, the GCC was similar across the groups (p = 0.0885). Additionally, RPCs inside the disc were significantly reduced in KC eyes after PKP compared to control eyes (p < 0.0001). A significant positive correlation was found between RPC whole vessel density and RNFL thickness as measured via angio-OCT (r = 0.308, p < 0.0001). Conclusions: This study found that the RPC density inside the disc is significantly reduced in keratoconus patients after penetrating keratoplasty, highlighting RPCs inside the disc as a potential diagnostic tool for further assessment of keratoconus. Full article
(This article belongs to the Special Issue New Advances in Keratoplasty)
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18 pages, 14132 KiB  
Article
Retinal Vascular and Structural Changes in the Murine Alzheimer’s APPNL-F/NL-F Model from 6 to 20 Months
by Lidia Sánchez-Puebla, Inés López-Cuenca, Elena Salobrar-García, María González-Jiménez, Alberto Arias-Vázquez, José A. Matamoros, Ana I. Ramírez, José A. Fernández-Albarral, Lorena Elvira-Hurtado, Takaomi C. Saido, Takashi Saito, Carmen Nieto-Vaquero, María I. Cuartero, María A. Moro, Juan J. Salazar, Rosa de Hoz and José M. Ramírez
Biomolecules 2024, 14(7), 828; https://doi.org/10.3390/biom14070828 - 10 Jul 2024
Cited by 1 | Viewed by 2495
Abstract
Alzheimer’s disease (AD) may manifest retinal changes preceding brain pathology. A transversal case-control study utilized spectral-domain OCT angiography (SD-OCTA) and Angio-Tool software 0.6a to assess retinal vascular structures and OCT for inner and outer retina thickness in the APPNL-F/NL-F AD model at [...] Read more.
Alzheimer’s disease (AD) may manifest retinal changes preceding brain pathology. A transversal case-control study utilized spectral-domain OCT angiography (SD-OCTA) and Angio-Tool software 0.6a to assess retinal vascular structures and OCT for inner and outer retina thickness in the APPNL-F/NL-F AD model at 6, 9, 12, 15, 17, and 20 months old. Comparisons to age-matched wild type (WT) were performed. The analysis focused on the three vascular plexuses using AngiooTool and on retinal thickness, which was represented with the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Compared to WT, the APPNL-F/NL-F group exhibited both vascular and structural changes as early as 6 months persisting and evolving at 15, 17, and 20 months. Significant vascular alterations, principally in the superficial vascular complex (SVC), were observed. There was a significant decrease in the vessel area and the total vessel length in SVC, intermediate, and deep capillary plexus. The inner retina in the APPNL-F/NL-F group predominantly decreased in thickness while the outer retina showed increased thickness in most analyzed time points compared to the control group. There are early vascular and structural retinal changes that precede the cognitive changes, which appear at later stages. Therefore, the natural history of the APPNL-F/NL-F model may be more similar to human AD than other transgenic models. Full article
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9 pages, 6596 KiB  
Case Report
Open-Heart Cardio-Thoracic Biological Valve Replacement Following Complicated Transcatheter Aortic Valve Implantation
by Aneta Klotzka, Patrycja Woźniak, Marcin Misterski, Michał Rodzki, Mateusz Puślecki, Marek Jemielity, Marek Grygier, Aleksander Araszkiewicz, Sylwia Iwańczyk and Piotr Buczkowski
J. Pers. Med. 2023, 13(5), 838; https://doi.org/10.3390/jpm13050838 - 16 May 2023
Viewed by 1793
Abstract
Transcatheter aortic valve implantation (TAVI) is currently becoming the method of choice in high-risk patients with severe aortic valve stenosis. Post-TAVI complications are more common owing to the increasing use of the method. The majority of TAVI complications derive from concomitant aortic stenosis [...] Read more.
Transcatheter aortic valve implantation (TAVI) is currently becoming the method of choice in high-risk patients with severe aortic valve stenosis. Post-TAVI complications are more common owing to the increasing use of the method. The majority of TAVI complications derive from concomitant aortic stenosis with moderate/severe aortic insufficiency, paravalvular leak, and atrioventricular block. The contemporary TAVI qualification process includes a thorough echocardiography and angio-CT of the aorta, which is crucial in assessing valve measurements, determining the position of the coronary arteries branching from the aorta, and choosing the optimal valve size. We present the case report of an 81-year-old patient admitted to our hospital because of exacerbation of the clinical condition and development of pulmonary edema a few days after TAVI. Despite the reduction of the initial leak, an echocardiographic examination revealed the remaining severe paravalvular aortic leakage. We performed open-heart cardio-thoracic surgery, explanted the TAVI valve, and implanted the biological prosthesis (Edwards Perimount Magna size 25). Introduction of new interventional treatment approaches and the availability of imaging tools have substantially reduced the incidence of significant paravalvular leak and offered a better prognosis for patients undergoing TAVI. Full article
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17 pages, 38912 KiB  
Article
Visualization of Organ-Specific Lymphatic Growth: An Efficient Approach to Labeling Molecular Markers in Cleared Tissues
by Carolin Christ and Zoltán Jakus
Int. J. Mol. Sci. 2023, 24(6), 5075; https://doi.org/10.3390/ijms24065075 - 7 Mar 2023
Cited by 4 | Viewed by 2634
Abstract
Organ-specific lymphatics are essential for the maintenance of healthy organ function and lymphatic dysfunction can lead to the development of various diseases. However, the precise role of those lymphatic structures remains unknown, mainly due to inefficient visualization techniques. Here, we present an efficient [...] Read more.
Organ-specific lymphatics are essential for the maintenance of healthy organ function and lymphatic dysfunction can lead to the development of various diseases. However, the precise role of those lymphatic structures remains unknown, mainly due to inefficient visualization techniques. Here, we present an efficient approach to visualizing organ-specific lymphatic growth. We used a modified CUBIC protocol to clear mouse organs and combined it with whole-mount immunostaining to visualize lymphatic structures. We acquired images using upright, stereo and confocal microscopy and quantified them with AngioTool, a tool for the quantification of vascular networks. Using our approach, we then characterized the organ-specific lymphatic vasculature of the Flt4kd/+ mouse model, showing symptoms of lymphatic dysfunction. Our approach enabled us to visualize the lymphatic vasculature of organs and to analyze and quantify structural changes. We detected morphologically altered lymphatic vessels in all investigated organs of Flt4kd/+ mice, including the lungs, small intestine, heart and uterus, but no lymphatic structures in the skin. Quantifications showed that these mice have fewer and dilated lymphatic vessels in the small intestine and the lungs. Our results demonstrate that our approach can be used to investigate the importance of organ-specific lymphatics under both physiological and pathophysiological conditions. Full article
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14 pages, 4504 KiB  
Article
A Novel Nomogram Based on Imaging Biomarkers of Shear Wave Elastography, Angio Planewave Ultrasensitive Imaging, and Conventional Ultrasound for Preoperative Prediction of Malignancy in Patients with Breast Lesions
by Guoqiang Guo, Jiaping Feng, Chunchun Jin, Xuehao Gong, Yihao Chen, Sihan Chen, Zhanghong Wei, Huahua Xiong and Jianghao Lu
Diagnostics 2023, 13(3), 540; https://doi.org/10.3390/diagnostics13030540 - 2 Feb 2023
Cited by 6 | Viewed by 1947
Abstract
Several studies have demonstrated the difficulties in distinguishing malignant lesions of the breast from benign lesions owing to overlapping morphological features on ultrasound. Consequently, we aimed to develop a nomogram based on shear wave elastography (SWE), Angio Planewave Ultrasensitive imaging (Angio PLUS (AP)), [...] Read more.
Several studies have demonstrated the difficulties in distinguishing malignant lesions of the breast from benign lesions owing to overlapping morphological features on ultrasound. Consequently, we aimed to develop a nomogram based on shear wave elastography (SWE), Angio Planewave Ultrasensitive imaging (Angio PLUS (AP)), and conventional ultrasound imaging biomarkers to predict malignancy in patients with breast lesions. This prospective study included 117 female patients with suspicious lesions of the breast. Features of lesions were extracted from SWE, AP, and conventional ultrasound images. The least absolute shrinkage and selection operator (Lasso) algorithms were used to select breast cancer-related imaging biomarkers, and a nomogram was developed based on six of the 16 imaging biomarkers. This model exhibited good discrimination (area under the receiver operating characteristic curve (AUC): 0.969; 95% confidence interval (CI): 0.928, 0.989) between malignant and benign breast lesions. Moreover, the nomogram also showed demonstrated good calibration and clinical usefulness. In conclusion, our nomogram can be a potentially useful tool for individually-tailored diagnosis of breast tumors in clinical practice. Full article
(This article belongs to the Special Issue Advanced Ultrasound Technologies for Diagnosis)
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18 pages, 898 KiB  
Review
Early Saphenous Vein Graft Aneurysm Rupture: A Not So-Late Complication. Case Report and Comprehensive Literature Review
by Eleonora Mezzetti, Aniello Maiese, Federica Spina, Fabio Del Duca, Alessandra De Matteis, Marco Di Paolo, Raffaele La Russa, Emanuela Turillazzi and Vittorio Fineschi
Biomedicines 2023, 11(1), 220; https://doi.org/10.3390/biomedicines11010220 - 14 Jan 2023
Cited by 3 | Viewed by 2141
Abstract
Background and Objectives: Saphenous vein graft (SVG) is a cardiac surgical practice used to create a cardiac bypass in cases of coronary artery obstruction. It consists of a surgical procedure that involves the creation of an aorto-coronary communication by a venous conduit (saphenous [...] Read more.
Background and Objectives: Saphenous vein graft (SVG) is a cardiac surgical practice used to create a cardiac bypass in cases of coronary artery obstruction. It consists of a surgical procedure that involves the creation of an aorto-coronary communication by a venous conduit (saphenous vein) to bypass coronary stenosis and allow cardiac revascularization. This practice can be affected by early and late complications. The most feared complication is graft aneurysm or pseudoaneurysm degeneration and rupture which are considered late complications. This paper presents a rare case of SVG aneurysmal rupture that occurred 24 h after surgery and a review of the literature to provide a general look at the state of knowledge. Materials and Methods: The systematic review was carried out using the guidelines according to the PRISMA method. Results: Cases of aneurysmal rupture have never been described prior to one month after surgery. The male sex and subjects under 45 are the most affected by this complication. Death occurs in less than half of the cases, being more frequent in young people. Performing a CT or angio-CT examination led to the diagnosis. Conclusions: It is impossible to estimate the implanted vessel’s quality, so postoperative follow-up is fundamental. Transesophageal ultrasound can be useful, and hematochemical tests are valuable early diagnostic tools, whrease CT and angio-CT can be useful even months after surgery. Forensic analysis should always perform an autopsy and graft histological examination. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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20 pages, 14831 KiB  
Article
Deep Semantic Segmentation of Angiogenesis Images
by Alisher Ibragimov, Sofya Senotrusova, Kseniia Markova, Evgeny Karpulevich, Andrei Ivanov, Elizaveta Tyshchuk, Polina Grebenkina, Olga Stepanova, Anastasia Sirotskaya, Anastasiia Kovaleva, Arina Oshkolova, Maria Zementova, Viktoriya Konstantinova, Igor Kogan, Sergey Selkov and Dmitry Sokolov
Int. J. Mol. Sci. 2023, 24(2), 1102; https://doi.org/10.3390/ijms24021102 - 6 Jan 2023
Cited by 4 | Viewed by 3277
Abstract
Angiogenesis is the development of new blood vessels from pre-existing ones. It is a complex multifaceted process that is essential for the adequate functioning of human organisms. The investigation of angiogenesis is conducted using various methods. One of the most popular and most [...] Read more.
Angiogenesis is the development of new blood vessels from pre-existing ones. It is a complex multifaceted process that is essential for the adequate functioning of human organisms. The investigation of angiogenesis is conducted using various methods. One of the most popular and most serviceable of these methods in vitro is the short-term culture of endothelial cells on Matrigel. However, a significant disadvantage of this method is the manual analysis of a large number of microphotographs. In this regard, it is necessary to develop a technique for automating the annotation of images of capillary-like structures. Despite the increasing use of deep learning in biomedical image analysis, as far as we know, there still has not been a study on the application of this method to angiogenesis images. To the best of our knowledge, this article demonstrates the first tool based on a convolutional Unet++ encoder–decoder architecture for the semantic segmentation of in vitro angiogenesis simulation images followed by the resulting mask postprocessing for data analysis by experts. The first annotated dataset in this field, AngioCells, is also being made publicly available. To create this dataset, participants were recruited into a markup group, an annotation protocol was developed, and an interparticipant agreement study was carried out. Full article
(This article belongs to the Collection Feature Papers in Molecular Informatics)
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16 pages, 2964 KiB  
Article
The Efficacy of HGF/VEGF Gene Therapy for Limb Ischemia in Mice with Impaired Glucose Tolerance: Shift from Angiogenesis to Axonal Growth and Oxidative Potential in Skeletal Muscle
by Iurii S. Stafeev I, Maria A. Boldyreva, Svetlana S. Michurina, Margarita Yu. Agareva, Arina V. Radnaeva, Mikhail Yu. Menshikov, Yu-Chen Hu, Pavel I. Makarevich and Yelena V. Parfyonova
Cells 2022, 11(23), 3824; https://doi.org/10.3390/cells11233824 - 29 Nov 2022
Cited by 3 | Viewed by 3167
Abstract
Background: Combined non-viral gene therapy (GT) of ischemia and cardiovascular disease is a promising tool for potential clinical translation. In previous studies our group has developed combined gene therapy by vascular endothelial growth factor 165 (VEGF165) + hepatocyte growth factor ( [...] Read more.
Background: Combined non-viral gene therapy (GT) of ischemia and cardiovascular disease is a promising tool for potential clinical translation. In previous studies our group has developed combined gene therapy by vascular endothelial growth factor 165 (VEGF165) + hepatocyte growth factor (HGF). Our recent works have demonstrated that a bicistronic pDNA that carries both human HGF and VEGF165 coding sequences has a potential for clinical application in peripheral artery disease (PAD). The present study aimed to test HGF/VEGF combined plasmid efficacy in ischemic skeletal muscle comorbid with predominant complications of PAD-impaired glucose tolerance and type 2 diabetes mellitus (T2DM). Methods: Male C57BL mice were housed on low-fat (LFD) or high-fat diet (HFD) for 10 weeks and metabolic parameters including FBG level, ITT, and GTT were evaluated. Hindlimb ischemia induction and plasmid administration were performed at 10 weeks with 3 weeks for post-surgical follow-up. Limb blood flow was assessed by laser Doppler scanning at 7, 14, and 21 days after ischemia induction. The necrotic area of m.tibialis anterior, macrophage infiltration, angio- and neuritogenesis were evaluated in tissue sections. The mitochondrial status of skeletal muscle (total mitochondria content, ETC proteins content) was assessed by Western blotting of muscle lysates. Results: At 10 weeks, the HFD group demonstrated impaired glucose tolerance in comparison with the LFD group. HGF/VEGF plasmid injection aggravated glucose intolerance in HFD conditions. Blood flow recovery was not changed by HGF/VEGF plasmid injection either in LFD or HFD conditions. GT in LFD, but not in HFD conditions, enlarged the necrotic area and CD68+ cells infiltration. However, HGF/VEGF plasmid enhanced neuritogenesis and enlarged NF200+ area on muscle sections. In HFD conditions, HGF/VEGF plasmid injection significantly increased mitochondria content and ETC proteins content. Conclusions: The current study demonstrated a significant role of dietary conditions in pre-clinical testing of non-viral GT drugs. HGF/VEGF combined plasmid demonstrated a novel aspect of potential participation in ischemic skeletal muscle regeneration, through regulation of innervation and bioenergetics of muscle. The obtained results made HGF/VEGF combined plasmid a very promising tool for PAD therapy in impaired glucose tolerance conditions. Full article
(This article belongs to the Special Issue Gene and Cell Therapy in Regenerative Medicine)
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14 pages, 1379 KiB  
Article
Post-COVID-19 Syndrome: Retinal Microcirculation as a Potential Marker for Chronic Fatigue
by Sarah Schlick, Marianna Lucio, Gerd Wallukat, Alexander Bartsch, Adam Skornia, Jakob Hoffmanns, Charlotte Szewczykowski, Thora Schröder, Franziska Raith, Lennart Rogge, Felix Heltmann, Michael Moritz, Lorenz Beitlich, Julia Schottenhamml, Martin Herrmann, Thomas Harrer, Marion Ganslmayer, Friedrich E. Kruse, Robert Lämmer, Christian Mardin and Bettina Hohbergeradd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2022, 23(22), 13683; https://doi.org/10.3390/ijms232213683 - 8 Nov 2022
Cited by 19 | Viewed by 10202
Abstract
Post-COVID-19 syndrome (PCS) is characterized by persisting sequelae after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PCS can affect patients with all COVID-19 disease severities. As previous studies have revealed impaired blood flow as a provoking factor triggering PCS, it was [...] Read more.
Post-COVID-19 syndrome (PCS) is characterized by persisting sequelae after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PCS can affect patients with all COVID-19 disease severities. As previous studies have revealed impaired blood flow as a provoking factor triggering PCS, it was the aim of the present study to investigate the potential association between self-reported chronic fatigue and retinal microcirculation in patients with PCS, potentially indicating an objective biomarker. A prospective study was performed, including 201 subjects: 173 patients with PCS and 28 controls. Retinal microcirculation was visualized by OCT angiography (OCT-A) and quantified using the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic fatigue (CF) was assessed according to the variables of Bell’s score, age and gender. VDs in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed, considering the repetitions (12 times). Seropositivity for autoantibodies targeting G protein-coupled receptors (GPCR-AAbs) was determined by an established cardiomyocyte bioassay. Taking account of the repetitions, a mixed model was performed to detect possible differences in the least square means between the different groups included in the analysis. An age effect in relation to VD was observed between patients and controls (p < 0.0001). Gender analysis showed that women with PCS showed lower VD levels in the SVP compared to male patients (p = 0.0015). The PCS patients showed significantly lower VDs in the ICP as compared to the controls (p = 0.0001 (CI: 0.32; 1)). Moreover, considering PCS patients, the mixed model revealed a significant difference between those with chronic fatigue (CF) and those without CF with respect to VDs in the SVP (p = 0.0033 (CI: −4.5; −0.92)). The model included variables of age, gender and Bell’s score, representing a subjective marker for CF. Consequently, retinal microcirculation might serve as an objective biomarker in subjectively reported chronic fatigue in patients with PCS. Full article
(This article belongs to the Special Issue Towards an Understanding of Retinal Diseases and Novel Treatment 2.0)
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13 pages, 2959 KiB  
Article
Vacuum-Implemented Removal of Lead Vegetations in Cardiac Device-Related Infective Endocarditis
by Vincenzo Tarzia, Matteo Ponzoni, Giuseppe Evangelista, Chiara Tessari, Emanuele Bertaglia, Manuel De Lazzari, Fabio Zanella, Demetrio Pittarello, Federico Migliore and Gino Gerosa
J. Clin. Med. 2022, 11(15), 4600; https://doi.org/10.3390/jcm11154600 - 7 Aug 2022
Cited by 9 | Viewed by 2734
Abstract
When approaching infected lead removal in cardiac device-related infective endocarditis (CDRIE), a surgical consideration for large (>20 mm) vegetations is recommended. We report our experience with the removal of large CDRIE vegetations using the AngioVac system, as an alternative to conventional surgery. We [...] Read more.
When approaching infected lead removal in cardiac device-related infective endocarditis (CDRIE), a surgical consideration for large (>20 mm) vegetations is recommended. We report our experience with the removal of large CDRIE vegetations using the AngioVac system, as an alternative to conventional surgery. We retrospectively reviewed all infected lead extractions performed with a prior debulking using the AngioVac system, between October 2016 and April 2022 at our institution. A total of 13 patients presented a mean of 2(1) infected leads after a mean of 5.7(5.7) years from implantation (seven implantable cardioverter-defibrillators, four cardiac resynchronization therapy-defibrillators, and two pacemakers). The AngioVac system was used as a venous–venous bypass in six cases (46.2%), venous–venous ECMO-like circuit (with an oxygenator) in five (38.5%), and venous–arterial ECMO-like circuit in two cases (15.4%). Successful (>70%) aspiration of the vegetations was achieved in 12 patients (92.3%) and an intraoperative complication (cardiac perforation) only occurred in 1 case (7.7%). Subsequent lead extraction was successful in all cases, either manually (38.5%) or using mechanical tools (61.5%). The AngioVac system is a promising effective and safe option for large vegetation debulking in CDRIE. Planning the extracorporeal circuit design may represent the optimal strategy to enhance the tolerability of the procedure and minimize adverse events. Full article
(This article belongs to the Special Issue Advances in Cardiac Electrophysiology and Pacing)
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17 pages, 3021 KiB  
Review
Gurltia paralysans: A Neglected Angio-Neurotropic Parasite of Domestic Cats (Felis catus) and Free-Ranging Wild Felids (Leopardus spp.) in South America
by Lisbeth Rojas-Barón, Anja Taubert, Carlos Hermosilla, Marcelo Gómez, Manuel Moroni and Pamela Muñoz
Pathogens 2022, 11(7), 792; https://doi.org/10.3390/pathogens11070792 - 13 Jul 2022
Cited by 1 | Viewed by 3916
Abstract
Gurltia paralysans is a neglected and re-emerging metastrongyloid angio-neurotropic nematode causing severe chronic meningomyelitis in domestic cats (Felis catus) as well as in free-ranging small wild felids such as kodkods (Leopardus guigna), margays (Leopardus wiedii) and the [...] Read more.
Gurltia paralysans is a neglected and re-emerging metastrongyloid angio-neurotropic nematode causing severe chronic meningomyelitis in domestic cats (Felis catus) as well as in free-ranging small wild felids such as kodkods (Leopardus guigna), margays (Leopardus wiedii) and the northern tiger cat (Leopardus triginus) in South America. Within these definitive hosts (DH), adult males and females of G. paralysans parasitize the leptomeningeal veins of the subarachnoid space and/or the meningeal veins of spinal cord parenchyma, inducing vascular alterations. Feline gurltiosis has been associated with progressive thrombophlebitis of the meningeal veins, resulting in ambulatory paraparesis, paraplegia, ataxia, hindlimb proprioceptive deficit, uni- or bilateral hyperactive patellar reflexes, faecal and urinary incontinence, and tail paralysis. The complete life cycle of G. paralysans has not been elucidated yet, but most probably involves gastropods as obligate intermediate hosts (IH). In terms of epidemiology, G. paralysans infections in domestic and wild felids are scattered around various South American countries, with hyperendemic areas in southern parts of Chile. Etiological diagnosis of G. paralysans still represents a challenge for clinicians due to a lack of evidence of the excretion of either eggs or larvae in faeces or in other body fluids. Diagnosis is based on clinical neurological signs, imaging findings through computed tomography (CT), myelography, magnetic resonance imaging (MRI), and post mortem examination. Nonetheless, novel diagnostic tools have been developed, including semi-nested PCR for detecting circulating G. paralysans DNA in the cerebrospinal fluid, serum and blood samples as well as in serological diagnostic kits detecting parasite-derived antigens, but these need validation for routine usage. The hypothetical life cycle of G. paralysans is addressed in this article, including the exogenous stages (i.e., eggs, and first- (L1), second- (L2) and third-stage (L3) larvae) and obligate gastropod IH and/or paratenic hosts (PH), and we propose possible anatomical migration routes of infective L3 that reach the leptomeningeal veins in vivo. Finally, the pro-inflammatory endothelium- and leukocyte-derived innate immune reactions of the host against G. paralysans, which most likely result in thrombophlebitis and meningomyelitis, are briefly touched on. Full article
(This article belongs to the Section Parasitic Pathogens)
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17 pages, 3378 KiB  
Article
Long COVID: Association of Functional Autoantibodies against G-Protein-Coupled Receptors with an Impaired Retinal Microcirculation
by Charlotte Szewczykowski, Christian Mardin, Marianna Lucio, Gerd Wallukat, Jakob Hoffmanns, Thora Schröder, Franziska Raith, Lennart Rogge, Felix Heltmann, Michael Moritz, Lorenz Beitlich, Julia Schottenhamml, Martin Herrmann, Thomas Harrer, Marion Ganslmayer, Friedrich E. Kruse, Martin Kräter, Jochen Guck, Robert Lämmer, Matthias Zenkel, Andreas Gießl and Bettina Hohbergeradd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2022, 23(13), 7209; https://doi.org/10.3390/ijms23137209 - 29 Jun 2022
Cited by 54 | Viewed by 16528
Abstract
Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and therapeutic options are limited, as the pathomechanism of LC is elusive. As the number of acute SARS-CoV-2 infections was and is [...] Read more.
Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and therapeutic options are limited, as the pathomechanism of LC is elusive. As the number of acute SARS-CoV-2 infections was and is large, LC will be a challenge for the healthcare system. Previous studies revealed an impaired blood flow, the formation of microclots, and autoimmune mechanisms as potential factors in this complex interplay. Since functionally active autoantibodies against G-protein-coupled receptors (GPCR-AAbs) were observed in patients after SARS-CoV-2 infection, this study aimed to correlate the appearance of GPCR-AAbs with capillary microcirculation. The seropositivity of GPCR-AAbs was measured by an established cardiomyocyte bioassay in 42 patients with LC and 6 controls. Retinal microcirculation was measured by OCT–angiography and quantified as macula and peripapillary vessel density (VD) by the Erlangen-Angio Tool. A statistical analysis yielded impaired VD in patients with LC compared to the controls, which was accentuated in female persons. A significant decrease in macula and peripapillary VD for AAbs targeting adrenergic β2-receptor, MAS-receptor angiotensin-II-type-1 receptor, and adrenergic α1-receptor were observed. The present study might suggest that a seropositivity of GPCR-AAbs can be linked to an impaired retinal capillary microcirculation, potentially mirroring the systemic microcirculation with consecutive clinical symptoms. Full article
(This article belongs to the Special Issue Towards an Understanding of Retinal Diseases and Novel Treatment 2.0)
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