The wet form of age-related macular degeneration is characterized by neovascular pathologies that, if untreated, can result in edemas followed by rapid vision loss. Inhibition of vascular endothelial growth factor (VEGF) has been used to successfully treat neovascular pathologies of the eye. Nonetheless, some patients require frequent intravitreal injections of anti-VEGF drugs, increasing the burden and risk of complications from the procedure to affected individuals. Recombinant adeno-associated virus (rAAV)-mediated expression of anti-VEGF proteins is an attractive alternative to reduce risk and burden to patients. However, controversy remains as to the safety of prolonged VEGF inhibition in the eye. Here, we show that two out of four rAAV serotypes tested by intravitreal delivery to express the anti-VEGF drug conbercept lead to a dose-dependent vascular sheathing pathology that is characterized by immune cell infiltrates, reminiscent of vasculitis in humans. We show that this pathology is accompanied by increased expression in vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM1), both of which promote extravasation of immune cells from the vasculature. While formation of the vascular sheathing pathology is prevented in immunodeficient Rag-1 mice that lack B and T cells, increased expression of VACM1 and ICAM1 still occurs, indicating that inhibition of VEGF function leads to expression changes in cell adhesion molecules that promote extravasation of immune cells. Importantly, a 10-fold lower dose of one of the vectors that cause a vascular sheathing pathology is still able to reduce edemas resulting from choroidal neovascularization without causing any vascular sheathing pathology and only a minimal increase in VCAM1 expression. The data suggest that treatments of neovascular eye pathologies with rAAV-mediated expression of anti VEGF drugs can be developed safely. However, viral load needs to be adjusted to the tropisms of the serotype and the expression pattern of the promoter.
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http://dx.doi.org/10.1089/hum.2021.132 | DOI Listing |
Sci Rep
January 2025
Department of Cardiology, Peking University International Hospital, Peking University, Beijing, 102206, China.
This study aims to assess the clinical efficacy and feasibility of the Perclose ProGlide Suture-Mediated Closure System (Abbott Vascular, Redwood City, CA, USA) for transbrachial access. A total of 100 patients from July 2020 to December 2023 were included in this retrospective study. Among them, 40 patients underwent ProGlide-guided suture closure following brachial artery (BA) puncture, while 60 patients received traditional manual compression.
View Article and Find Full Text PDFA A Pract
January 2025
Département d'Anesthésie, Hôpital Antoine Béclère, APHP.Université Paris-Saclay, Clamart, France.
We describe a patient with severe Arnold Chiari Malformation and syringomyelia who underwent gynecological laparoscopy in an emergency context; no brain imaging was available. We here report the successful use of optic nerve sheath diameter (ONSD) and middle cerebral artery (MCA) velocity measurements as surrogate monitoring for cerebral blood flow and intracranial pressure, respectively. MCA velocity was low when assessed after peritoneal insufflation and ONSD increased to 6.
View Article and Find Full Text PDFJ Thorac Cardiovasc Surg
January 2025
Department of Surgery, Division of Vascular Surgery, University of Maryland School of Medicine.
Objective: We present our experience with endovascular Bentall procedure (Endo-Bentall) using a modular valve conduit (Endo-Bentall) in high-risk patients with aortic root pathologies.
Methods: The physician constructed Endo-Bentall device is composed of a self-expanding transcatheter aortic valve (TAVR), aortic endovascular stent graft (TEVAR), and two wire-reinforced fenestrations for coronary artery stenting. The TAVR valve is sutured into an appropriately sized TEVAR graft.
Ultrasound J
January 2025
Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
Background: There are significant discrepancies in the optic nerve sheath diameter (ONSD) reported in the literature. We aimed to determine the ultrasonographic imaging features of ONSD and ophthalmic vessels in a healthy population, using a standardized protocol, and to estimate the effect of demographics and positioning changes on imaging measurements.
Methods: We measured the mean values of the ONSD in supine and sitting position and the Doppler imaging parameters of the ophthalmic, central retinal and short posterior ciliary arteries.
BMC Cardiovasc Disord
January 2025
Heart Center, Women and Children's Hospital, Qingdao University, 6 Tongfu Road, Qingdao, 266034, Shandong, China.
Objectives: To evaluate the efficacy and safety of purse-string sutures (PSS) compared with manual compression for access hemostasis in children with atrial septal defects (ASDs) after large-caliber venous delivery sheaths removal.
Methods: We conducted a retrospective clinical data review of 271 children with ASDs who underwent transcatheter device closure through large-caliber venous delivery sheaths (≥ 8 Fr) at our institution from January 2018 to January 2023. The PSS group (n = 144) was compared to the control group (n = 127), which underwent manual compression for femoral venous hemostasis after sheath removal, focusing on hemostatic time, limb braking time, bed rest time, hospital stay, and vascular access complications.
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