Abnormal Vessels Research Articles

The impact of elevated lipoprotein a levels on retinal vein occlusion in young individual: Case report with 7 months follow‐up

Aims/Purpose: Branch retinal vein occlusion (BRVO) occurs when a branch of the retinal vein becomes obstructed. The aim of this study case was to provide insights into the potential role of Lipoprotein (Lp) (a) in the pathogenesis of BRVO.Methods: Case of a 47‐year‐old woman with no significant ophthalmological or general medical history, except the use of oral contraception and smoking habits. Presented to the emergency care after 5 days of experiencing a sudden vision loss in her right eye.Results: The ophthalmological examination revealed a visual acuity of 10/10 on the left (OS) and VBLM/10 on the right eye (OD). Slit lamp and Fundus examination showed on OD a relative afferent pupillary defect and the classic features of acute retinal branch vein occlusion, including tortuous veins, capillary occlusion, papillary and macular oedema and haemorrhages. While all was normal in OS. A comprehensive ophthalmic examination was conducted, including fluorescein angiography and optical coherent tomography that showed no abnormal vessel growth at this stage. Then, the indication for a dexamethasone intravitreal implant has been made along with panretinal photocoagulation (PRP) in the ischaemic areas. More, discontinuing oral contraception, the serum concentrations of specific antibodies, as anticardiolipin and antiphospholipids, as well as homocysteine and Lp (a) levels. The blood tests yielded negative results except for the abnormal plasma level of lipoprotein (a), which was measured at 900 mg/L. After 2 months of follow‐up. The visual acuity in OD was measured at 9/10. Moreover, the restoration of normal macular thickness after 4 months. However, at 6 months follow‐up, the appearance of a neovascularization adjacent to the previously laser‐treated area. As a result, a series of closely spaced PRP was performed along with an intravitreal anti‐vascular endothelial growth factor. After 1 month, a complete disappearance of the neovascularization was observed.Conclusions: Identification of independent and highly predictive risk factors for BRVO is still a big challenge. The main goals are the preservation of visual acuity and the prevention of relapses. This case report emphasizes the importance of incorporating a systematic Lp (a) testing into clinical practice, even in young individual.

Preserving sight: Managing and preventing diabetic retinopathy

Abstract Preserving eyesight in the presence of diabetic retinopathy, a subtle complication of diabetes, requires a proactive and comprehensive approach. This condition, characterized by the gradual deterioration of the blood vessels in the retina, can quietly advance and pose a significant threat to vision. Effectively managing this issue involves careful control of blood glucose levels through medications, dietary choices, and physical activity. By preventing prolonged high blood sugar levels, the main culprit behind retinal damage, individuals can slow down the progression of diabetic retinopathy and minimize its impact on vision. Medical interventions, such as laser therapies and anti-vascular endothelial growth factor injections, offer targeted measures to address abnormal blood vessel growth and leakage. Regular eye assessments are crucial, providing early detection opportunities even in the absence of obvious symptoms and allowing for timely intervention before irreversible damage occurs. Prevention is equally important, emphasizing proactive measures to avoid diabetic retinopathy. Monitoring blood pressure and lipid levels, along with adopting a health-conscious lifestyle, strengthens cardiovascular health, indirectly protecting the fragile retinal blood vessels. By following diabetes management protocols, maintaining a balanced diet, engaging in regular physical activity, and avoiding tobacco use, individuals can significantly reduce their vulnerability to diabetic retinopathy. Combined with efforts to increase community awareness and educate about the importance of regular eye check-ups, this comprehensive approach empowers individuals to actively manage their eye health, ultimately preserving the precious gift of sight.

Metformin promotes the normalization of abnormal blood vessels after radiofrequency ablation deficiency in hepatocellular carcinoma by microRNA-302b-3p targeting thioredoxin-interacting protein

Metformin has shown great promise in the treatment of HCC. Radiofrequency ablation (RFA) deficiency results in recurrence and metastasis of remaining HCC tumors. Here, we aimed to investigate the role and mechanism of metformin in HCC after RFA deficiency. HCC cell line Hep-G2 was selected to simulate RFA deficiency and named HepG2-H cells. After treating cells with different concentrations of metformin (2.5, 5, 10 μM) or transfecting related plasmids, cell proliferation, migration, invasion, apoptosis and angiogenesis were detected, in vitro permeability test was performed, and an angiogenesis-related protein VEGFA was analyzed. The residual HCC model after RFA deficiency was established in mice. Metformin was administered by gavage to detect changes in tumor volume and weight, and CD31 staining was used to observe microvessels. The targeting relationship between miR-302b-3p and TXNIP was demonstrated by the bioinformatics website, dual-luciferase reporter assay, and RNA pull-down assay. The results found that metformin inhibited RFA deficiency-induced growth and angiogenesis of HCC cells in vitro. miR-302b-3p counteracted the therapeutic effect of metformin on RFA deficiency. miR-302b-3p targeted regulation of TXNIP. The up-regulation of TXNIP reversed the effects of overexpression of miR-302b-3p on RFA-deficient HCC cells. Metformin inhibited RFA-deficiency-induced HCC growth and tumor vascular abnormalities in vivo. Overall, metformin promotes the normalization of abnormal blood vessels after RFA deficiency in HCC by miR-302b-3p targeting TXNIP, which can be used to prevent the progression of HCC after RFA.

Metformin promotes the normalization of abnormal blood vessels after radiofrequency ablation deficiency in hepatocellular carcinoma by microRNA-302b-3p targeting thioredoxin-interacting protein.

Metformin has shown great promise in the treatment of HCC. Radiofrequency ablation (RFA) deficiency results in recurrence and metastasis of remaining HCC tumors. Here, we aimed to investigate the role and mechanism of metformin in HCC after RFA deficiency. HCC cell line Hep-G2 was selected to simulate RFA deficiency and named HepG2-H cells. After treating cells with different concentrations of metformin (2.5, 5, 10 μM) or transfecting related plasmids, cell proliferation, migration, invasion, apoptosis and angiogenesis were detected, in vitro permeability test was performed, and an angiogenesis-related protein VEGFA was analyzed. The residual HCC model after RFA deficiency was established in mice. Metformin was administered by gavage to detect changes in tumor volume and weight, and CD31 staining was used to observe microvessels. The targeting relationship between miR-302b-3p and TXNIP was demonstrated by the bioinformatics website, dual-luciferase reporter assay, and RNA pull-down assay. The results found that metformin inhibited RFA deficiency-induced growth and angiogenesis of HCC cells in vitro. miR-302b-3p counteracted the therapeutic effect of metformin on RFA deficiency. miR-302b-3p targeted regulation of TXNIP. The up-regulation of TXNIP reversed the effects of overexpression of miR-302b-3p on RFA-deficient HCC cells. Metformin inhibited RFA-deficiency-induced HCC growth and tumor vascular abnormalities in vivo. Overall, metformin promotes the normalization of abnormal blood vessels after RFA deficiency in HCC by miR-302b-3p targeting TXNIP, which can be used to prevent the progression of HCC after RFA.

Machine Learning Approach for Analyzing 3-Year Outcomes of Patients with Brain Arteriovenous Malformation (AVM) after Stereotactic Radiosurgery (SRS).

A cerebral arteriovenous malformation (AVM) is a tangle of abnormal blood vessels that irregularly connects arteries and veins. Stereotactic radiosurgery (SRS) has been shown to be an effective treatment for AVM patients, but the factors associated with AVM obliteration remains a matter of debate. In this study, we aimed to develop a model that can predict whether patients with AVM will be cured 36 months after intervention by means of SRS and identify the most important predictors that explain the probability of being cured. A machine learning (ML) approach was applied using decision tree (DT) and logistic regression (LR) techniques on historical data (sociodemographic, clinical, treatment, angioarchitecture, and radiosurgery procedure) of 202 patients with AVM who underwent SRS at the Instituto de Radiocirugía del Perú (IRP) between 2005 and 2018. The LR model obtained the best results for predicting AVM cure with an accuracy of 0.92, sensitivity of 0.93, specificity of 0.89, and an area under the curve (AUC) of 0.98, which shows that ML models are suitable for predicting the prognosis of medical conditions such as AVM and can be a support tool for medical decision-making. In addition, several factors were identified that could explain whether patients with AVM would be cured at 36 months with the highest likelihood: the location of the AVM, the occupation of the patient, and the presence of hemorrhage.

Unsupervised maritime anomaly detection for intelligent situational awareness using AIS data

With the mandatory implementation of the automatic identification system and the rapid advancement of relevant satellite communication technologies, a vast amount of vessel trajectory data has been amassed. It has catalyzed advancements in the field of maritime anomaly detection, significantly contributing to the enhancement of intelligent maritime situational awareness. However, detecting abnormal vessel trajectories from massive data is a highly challenging task that requires extensive manual effort. To address the challenge, this paper develops an unsupervised deep learning method for detecting abnormal vessel trajectories. Specifically, we first generate the informative trajectory images by remapping the raw vessel trajectories into two-dimensional matrices while maintaining the spatio-temporal properties. Then, a Wasserstein generative adversarial network with gradient penalty (WGAN-GP) is trained on normal vessel trajectories. Next, an encoder is trained to map these trajectory images to a latent space. Finally, the trained encoder and WGAN-GP are used to design an anomaly score for detecting abnormal vessel trajectories and anomalies in vessel trajectories. Experimental evaluations using multiple evaluation metrics on diverse simulated and real-world maritime environments validate the efficacy of the proposed method in unsupervised maritime anomaly detection. The results indicate that the proposed model can provide accurate anomaly detection on vessel trajectories without manual labeling.

Requirement of Site-Specific Tyrosine Phosphorylation of Cortactin in Retinal Neovascularization and Vascular Leakage.

Retinal neovascularization is a major cause of vision impairment. Therefore, the purpose of this study is to investigate the mechanisms by which hypoxia triggers the development of abnormal and leaky blood vessels. A variety of cellular and molecular approaches as well as tissue-specific knockout mice were used to investigate the role of Cttn (cortactin) in retinal neovascularization and vascular leakage. We found that VEGFA (vascular endothelial growth factor A) stimulates Cttn phosphorylation at Y421, Y453, and Y470 residues in human retinal microvascular endothelial cells. In addition, we observed that while blockade of Cttn phosphorylation at Y470 inhibited VEGFA-induced human retinal microvascular endothelial cell angiogenic events, suppression of Y421 phosphorylation protected endothelial barrier integrity from disruption by VEGFA. In line with these observations, while blockade of Cttn phosphorylation at Y470 negated oxygen-induced retinopathy-induced retinal neovascularization, interference with Y421 phosphorylation prevented VEGFA/oxygen-induced retinopathy-induced vascular leakage. Mechanistically, while phosphorylation at Y470 was required for its interaction with Arp2/3 and CDC6 facilitating actin polymerization and DNA synthesis, respectively, Cttn phosphorylation at Y421 leads to its dissociation from VE-cadherin, resulting in adherens junction disruption. Furthermore, whereas Cttn phosphorylation at Y470 residue was dependent on Lyn, its phosphorylation at Y421 residue required Syk activation. Accordingly, lentivirus-mediated expression of shRNA targeting Lyn or Syk levels inhibited oxygen-induced retinopathy-induced retinal neovascularization and vascular leakage, respectively. The above observations show for the first time that phosphorylation of Cttn is involved in a site-specific manner in the regulation of retinal neovascularization and vascular leakage. In view of these findings, Cttn could be a novel target for the development of therapeutics against vascular diseases such as retinal neovascularization and vascular leakage.

Succinate-induced macrophage polarization and RBP4 secretion promote vascular sprouting in ocular neovascularization

Pathological neovascularization is a pivotal biological process in wet age-related macular degeneration (AMD), retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR), in which macrophages (Mφs) play a key role. Tip cell specialization is critical in angiogenesis; however, its interconnection with the surrounding immune environment remains unclear. Succinate is an intermediate in the tricarboxylic acid (TCA) cycle and was significantly elevated in patients with wet AMD by metabolomics. Advanced experiments revealed that SUCNR1 expression in Mφ and M2 polarization was detected in abnormal vessels of choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR) models. Succinate-induced M2 polarization via SUCNR1, which facilitated vascular endothelial cell (EC) migration, invasion, and tubulation, thus promoting angiogenesis in pathological neovascularization. Furthermore, evidence indicated that succinate triggered the release of RBP4 from Mφs into the surroundings to regulate endothelial sprouting and pathological angiogenesis via VEGFR2, a marker of tip cell formation. In conclusion, our results suggest that succinate represents a novel class of vasculature-inducing factors that modulate Mφ polarization and the RBP4/VEGFR2 pathway to induce pathological angiogenic signaling through tip cell specialization.Graphical

Robot-assisted transposition of aberrant lower polar renal vessels in a 14-year-old child with vasorenal hydrophnerosis

This study presents a patient with pyeloureteral segment obstruction caused by aberrant inferior polar vessels using the robotic Hellström – Chapman procedure and reports its short-term results. A 14-year-old girl was admitted to Irkutsk Regional Children’s Clinical Hospital because of obstruction of the pyeloureteral junction caused by external compression by aberrant lower polar vessels. The diagnosis was established by ultrasonography and Doppler sonography and confirmed by contrasted computed tomography. Surgery was performed using the Versius surgical robot manufactured by CMR (UK). Delicate actions were used to mobilize the abnormal vessels and move them to the anterior wall of the pelvis. Then, they were “wrapped” with the anterior wall of the pelvis. Postoperative follow-up included clinical evaluation and renal ultrasound examination 1, 3, and 6 months after surgery. The operative duration was 65 min. During the robot-assisted Hellström – Chapman operation, no intraoperative complications, such as damage to the vessels supplying the kidney and neighboring organs, were noted. The patient did not require internal or external drainage of the upper urinary tract or perinephric space. The anteroposterior diameter of the pelvis decreased from 30 to 8 mm. The resistive index of the blood flow in the renal vessels decreased from 0.74 to 0.58. The Hellström – Chapman robotic procedure is a safe and effective procedure for the correction of vasorenal hydronephrosis. However, this surgery requires patient selection to ensure future treatment success.

PERPLEXING IMPACTED THIRD MOLARS IN A CASE OF TRIGEMINAL NEURALGIA AND ARACHNOID CYST (CASE REPORT)

Introduction: Trigeminal neuralgia (TN) is the most frequent form of craniofacial neuropathic pain, with a wide range of severity. Trigeminal neuralgia classically has been associated with neurovascular compression in the prepontine cistern at the nerve root entry zone or in Meckel’s cave due to an abnormal vessel, tumor, or cyst. Arachnoid cysts of the posterior cranial fossa are still less commonly compared to those superior to the constituent part of the posterior cranial fossa meninges. However, the arachnoid cyst in conjunction with the impacted third molar may cause compression of the trigeminal ganglion with similar clinical symptoms. The aim of this report is to explain the management of the first division of trigeminal neuralgia with an arachnoid cyst perplexed by impacted third molars. Case report: A case of a 27-year-old female with throbbing pain on top of her head, forehead, temple, and eyes several times. Extensive clinical and radiologic examinations were performed and revealed an arachnoid cyst and impacted third molars. Impacted third molars were removed. The patient declined the surgery for the arachnoid cyst and was treated symptomatically with amitriptyline 25 mg once daily until recently. The definitive diagnosis was the first division of trigeminal neuralgia and an arachnoid cyst. Conclusions A fundamental aspect of the diagnosis of trigeminal neuralgia is to examine and exclude all possible underlying etiologies and structural pathologies, which can refer the pain to a location remote from the stimulus.

Level-set based adaptive-active contour segmentation technique with long short-term memory for diabetic retinopathy classification.

Diabetic Retinopathy (DR) is a major type of eye defect that is caused by abnormalities in the blood vessels within the retinal tissue. Early detection by automatic approach using modern methodologies helps prevent consequences like vision loss. So, this research has developed an effective segmentation approach known as Level-set Based Adaptive-active Contour Segmentation (LBACS) to segment the images by improving the boundary conditions and detecting the edges using Level Set Method with Improved Boundary Indicator Function (LSMIBIF) and Adaptive-Active Counter Model (AACM). For evaluating the DR system, the information is collected from the publically available datasets named as Indian Diabetic Retinopathy Image Dataset (IDRiD) and Diabetic Retinopathy Database 1 (DIARETDB 1). Then the collected images are pre-processed using a Gaussian filter, edge detection sharpening, Contrast enhancement, and Luminosity enhancement to eliminate the noises/interferences, and data imbalance that exists in the available dataset. After that, the noise-free data are processed for segmentation by using the Level set-based active contour segmentation technique. Then, the segmented images are given to the feature extraction stage where Gray Level Co-occurrence Matrix (GLCM), Local ternary, and binary patterns are employed to extract the features from the segmented image. Finally, extracted features are given as input to the classification stage where Long Short-Term Memory (LSTM) is utilized to categorize various classes of DR. The result analysis evidently shows that the proposed LBACS-LSTM achieved better results in overall metrics. The accuracy of the proposed LBACS-LSTM for IDRiD and DIARETDB 1 datasets is 99.43% and 97.39%, respectively which is comparably higher than the existing approaches such as Three-dimensional semantic model, Delimiting Segmentation Approach Using Knowledge Learning (DSA-KL), K-Nearest Neighbor (KNN), Computer aided method and Chronological Tunicate Swarm Algorithm with Stacked Auto Encoder (CTSA-SAE).

GM-CSF Promotes the Development of Dysfunctional Vascular Networks in Moyamoya Disease.

Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with the development of a network of abnormal vessels. Immune inflammation is associated with the occurrence and development of MMD. However, the mechanisms underlying the formation of the abnormal vascular network remain unclear. Twenty-eight patients with MMD, 26 ischemic stroke patients, and 26 unrelated healthy volunteers were enrolled in this study The data showed that the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) were higher in MMD patients than in healthy controls (P <0.01), and GM-CSF was mainly from Th1 and Th17 cells in MMD. We found that increased GM-CSF drove monocytes to secrete a series of cytokines associated with angiogenesis, inflammation, and chemotaxis. In summary, our findings demonstrate for the first time the important involvement of GM-CSF in MMD and that GM-CSF is an important factor in the formation of abnormal vascular networks in MMD.

Targeting vascular normalization: a promising strategy to improve immune-vascular crosstalk in cancer immunotherapy.

Blood vessels are a key target for cancer therapy. Compared with the healthy vasculature, tumor blood vessels are extremely immature, highly permeable, and deficient in pericytes. The aberrantly vascularized tumor microenvironment is characterized by hypoxia, low pH, high interstitial pressure, and immunosuppression. The efficacy of chemotherapy, radiotherapy, and immunotherapy is affected by abnormal blood vessels. Some anti-angiogenic drugs show vascular normalization effects in addition to targeting angiogenesis. Reversing the abnormal state of blood vessels creates a normal microenvironment, essential for various cancer treatments, specifically immunotherapy. In addition, immune cells and molecules are involved in the regulation of angiogenesis. Therefore, combining vascular normalization with immunotherapy may increase the efficacy of immunotherapy and reduce the risk of adverse reactions. In this review, we discussed the structure, function, and formation of abnormal vessels. In addition, we elaborated on the role of the immunosuppressive microenvironment in the formation of abnormal vessels. Finally, we described the clinical challenges associated with the combination of immunotherapy with vascular normalization, and highlighted future research directions in this therapeutic area.

Insights into the Tumor Microenvironment-Components, Functions and Therapeutics.

Similarly to our healthy organs, the tumor tissue also constitutes an ecosystem. This implies that stromal cells acquire an altered phenotype in tandem with tumor cells, thereby promoting tumor survival. Cancer cells are fueled by abnormal blood vessels, allowing them to develop and proliferate. Tumor-associated fibroblasts adapt their cytokine and chemokine production to the needs of tumor cells and alter the peritumoral stroma by generating more collagen, thereby stiffening the matrix; these processes promote epithelial-mesenchymal transition and tumor cell invasion. Chronic inflammation and the mobilization of pro-tumorigenic inflammatory cells further facilitate tumor expansion. All of these events can impede the effective administration of tumor treatment; so, the successful inhibition of tumorous matrix remodeling could further enhance the success of antitumor therapy. Over the last decade, significant progress has been made with the introduction of novel immunotherapy that targets the inhibitory mechanisms of T cell activation. However, extensive research is also being conducted on the stromal components and other cell types of the tumor microenvironment (TME) that may serve as potential therapeutic targets.

Preliminary experience with transcatheter closure of wind-sock-like perimembranous ventricular septal defects using Amplatzer Vascular Plug IV devices.

Amplatzer Vascular Plug IV (Abbott, USA) is usually used for the occlusion of abnormal tortuous vessels and has not been tried for the transcatheter closure of perimembranous ventricular septal defects with wind-sock morphology. Here, we report on three successful cases of perimembranous ventricular septal defect transcatheter closure using Amplatzer Vascular Plug IV. We did not observe residual shunting or new onset of complications during follow up. These preliminary positive results advocate the application and suitability of Amplatzer Vascular Plug IV for closing wind-sock-like perimembranous ventricular septal defects.

A Feasibility Study Evaluating Von Willebrand Factor in Patients with Gastrointestinal Angiodysplasia

Background: Abnormalities of von Willebrand Factor (VWF), such as those found in von Willebrand Disease (VWD) are associated with the development of abnormal blood vessels known as angiodysplasia. Angiodysplasia occurs primarily in the gastrointestinal (GI) tract, particularly the small bowel. Among patients with VWD, angiodysplasia is significantly overrepresented as a cause of GI bleeding and occurs in all VWD subtypes although it is reported more frequently in those with loss of the high molecular weight multimer of VWF. Recent studies have demonstrated more than a third of patients with VWD and GI bleeding have angiodysplasia when systematically assessed with Video Capsule Endoscopy (VCE) to examine the small bowel. Given the relationship between angiodysplasia and VWD our objective was to assess the feasibility of evaluating patients with GI angiodysplasia for abnormalities of VWF. Methods: We undertook a prospective single center pilot study to assess patients over the age of 18 with GI angiodysplasia for underlying abnormalities of VWF. Patients were identified based on angiodysplasia being present on a VCE study. Patients who consented to enrollment completed a self-administered bleeding assessment tool (BAT) as well as baseline demographic data. VWF testing included VWF antigen (VWF:Ag), VWF functional assay (VWF:GPIbM), Factor VIII coagulant activity (FVIII:C), and VWF pro-peptide (VWFpp) levels. Results: After reviewing 190 consecutive VCE studies performed at our institution between April 2021 and April 2023, we identified 50 patients who had capsule endoscopies demonstrating angiodysplasia of the GI tract. Thirteen of these patients consented to enrollment in the study. The bleeding histories of included patients are detailed in Table 1 along with their baseline clinical, laboratory, and demographic data. Two patients endorsed lifelong bleeding symptoms and three reported a significant family history of bleeding - all in a female relative. ISTH-BAT scores ranged from 0 to 18 with a median score of 2. Since our population is older than other studies that report on bleeding scores, we considered an abnormal bleeding score to be &amp;gt;6 as recent evidence indicates normal BAT scores increase over time. Five patients (38.6%) in our study had an ISTH-BAT abnormal bleeding score. VWF levels were assessed (Table 1) and one patient aged 88 years old with a significant family and lifelong history of bleeding received a new diagnosis of Type 2A VWD. Severe iron deficiency anemia requiring ongoing IV iron was diagnosed in two patients. Conclusion: In our feasibility study, we demonstrated a feasible protocol for recruitment of patients with GI angiodysplasia for clinical and laboratory testing of VWF. A significant proportion of our patients (38.6%) had abnormal bleeding scores and one patient had an underlying Type 2A VWD diagnosis.

Intravenous 3K3A-Activated Protein C Inhibits Murine Ocular Inflammation and Suppresses Ocular Choroidal Neovascularization

Introduction: Choroidal neovascularization (CNV) is characterized by the growth of newly formed abnormal blood vessels from the choroid extending into the neurosensory retina, leading to vision loss. CNV is a common cause of visual impairment in neovascular age-related macular degeneration (nAMD) patients. Current treatments failed to stop the continuity of the neurodegenerative process. Despite the urgency, no neuroprotective agent has been found yet to treat AMD and other neurodegenerative ocular diseases. 3K3A-activated protein C (APC) is a cell-signaling analog of the endogenous blood serine protease APC. Preclinical studies showed that circulating plasma 3K3A-APC readily crosses the blood-brain barrier (BBB) and reaches neurons due to EPCR-dependent transport. In rodent models of stroke, brain injury, and neurodegenerative disorders, 3K3A-APC exerts neuroprotective, anti-inflammatory, and vasculoprotective activities. Due to its pleiotropic effects, 3K3A-APC has advanced to clinical trial stages for treating acute brain damage and chronic neurodegenerative diseases, which share similarities with retinal neurodegenerative disorders. Notably, the retina is part of the central nervous system (CNS), and the blood-retina barrier shares functional and structural similarities with the BBB. We previously demonstrated that intraocular administration of 3K3A-APC functions as a pleiotropic cytoprotective molecule within the retina, reducing ocular inflammation, suppressing CNV growth, and exhibiting promising therapeutic potential as a neuroprotective agent for treating ocular disorders. Intraocular administration is commonly utilized for delivering therapeutics to treat retinal conditions. However, safety concerns, the burden on the healthcare system, and patient comfort may indicate that systemic administration of 3K3A-APC is a beneficial alternative. Aim: To determine whether intravenously injecting 3K3A-APC into mice tails will cross the blood-retina barrier, induce anti-inflammatory activities in the retina, and suppress CNV. Methods: The efficacy of systemic administration of 3K3A-APC was evaluated using two C57BL/6J murine models: the LPS-induced ocular inflammation and the laser-induced CNV model. CNV was triggered by laser and ocular inflammation was triggered by intravitreal injection of lipopolysaccharide (LPS). Murine recombinant 3K3A-APC was administered systemically via tail injection. Fluorescein isothiocyanate (FITC)-dextran perfusion followed by retinal flatmount staining with anti-CD11b was used to assess inflammatory co-localization of cells to retinal vessels. FITC-dextran perfusion followed by retinal pigment epithelium (RPE)-choroid flatmount was used to assess CNV vascular penetration using 3D confocal imaging. Results: LPS injection triggered robust inflammatory cell infiltration in both the anterior and posterior chambers of the eyes. Systemic administration of 3K3A-APC (0.5 mg/kg, 1 and 4 hours post-LPS) significantly inhibited ocular inflammation. Immunostaining performed 24 hours post LPS revealed that 3K3A-APC reduced the number of CD11b+ monocyte and their extravasation into the retinal parenchyma (Figure). In the laser-induced CNV model, systemic administration of 0.2 mg/kg 3K3A-APC was applied one hour and four days post-laser. Evaluation of retinal specimens ten days post-laser showed that 3K3A-APC treatment significantly suppressed CNV growth, attenuated the abnormal growth of blood vessels from the choroid into the sensory retina, and decreased myeloid cell recruitment to the RPE-choroid area. Conclusion: Our study reveals that systemically administered 3K3A-APC effectively inhibits ocular inflammation and reduces CNV formation. Drawing insights from the neuroprotective activities of 3K3A-APC in the brain and CNS and recognizing the retina, particularly the macula, as an extension of the brain, we propose 3K3A-APC as a potential neuroprotective treatment for AMD and other neurodegenerative retinal pathologies. Given the established safety of systemic 3K3A-APC administration in phase 2 clinical trials for ischemic stroke, our findings support further exploring 3K3A-APC as a novel therapeutic approach in ophthalmology. Further research is warranted to elucidate fully the mechanisms underlying 3K3A-APC's beneficial effects on the retina.

Hypertrophic Cardiomyopathy—Septal Perforator Arteries Doppler Flow Dynamics

Patients with hypertrophic cardiomyopathy (HCM) have been shown to exhibit abnormal diastolic vessel flow; however, flow pattern profiles and their possible association with different grades of diastolic dysfunction have not been studied. Color Doppler two-dimensional echocardiography permits visualization of the septal perforator arteries, and pulsed-wave Doppler allows recording of diastolic septal artery flow (SAF). Through routine visualization of the septal perforator arteries and acquisition of SAF, we noticed 3 patterns of SAF in patients with HCM. In this study, we aimed to assess the feasibility of the acquisition of SAF and to describe types of SAF in an HCM cohort and their associations with diastolic function. We reviewed two-dimensional echocardiograms and the electronic records of 108 patients with HCM in whom septal artery color and spectral Doppler had been performed. The peak diastolic and end-diastolic velocities, diastolic slope, diastolic flow time-velocity integral, and systolic flow reversal of the septal perforator arteries were recorded with pulsed-wave Doppler. Echocardiographic and clinical characteristics were analyzed. A reproducible pulsed-wave Doppler tracing was recorded in 54% of patients with HCM. Three distinct patterns of SAF were identified: type 1-smooth, linear holodiastolic velocity decrease; type 2-with presence of an atrial dip; and type 3-biphasic velocity decrease with an early, rapid diastolic slope and a mid-to-late gentle slope. These 3 SAFs correlated with different grades of diastolic dysfunction. Septal artery flow could be detected in more than 50% of patients with HCM. Three distinct types of SAF were identified, correlating with different grades of diastolic dysfunction. These 3 types of SAF can provide additional information about left ventricular end-diastolic pressure and diastolic function in patients with HCM in whom diastolic function may be difficult to determine.

Computed tomography-based imaging biomarker identifies coal workers’ pneumoconiosis

Rationale: The increase in the incidence and the diagnostic limitations of pneumoconiosis have emerged as a public health concern. This study aimed to conduct a computed tomography (CT)- based quantitative analysis to understand differences in imaging results of pneumoconiosis according to disease severity.Methods: According to the International Labor Organization (ILO) guidelines, coal workers’ pneumoconiosis (CWP) are classified into five categories. CT images were obtained only at full inspiration and were quantitatively evaluated for airway structural variables such as bifurcation angle (θ), hydraulic diameter (Dh), wall thickness (WT), and circularity (Cr). Parenchymal functional variables include abnormal regions (emphysema, ground–glass opacities, consolidation, semi consolidation, and fibrosis) and blood vessel volume. Through the propensity score matching method, the confounding effects were decreased.Results: Category 4 demonstrated a reduced θ in TriLUL, a thicker airway wall in both the Trachea and Bronint compared to Category 0, and a decreased Cr in Bronint. Category 4 presented with higher abnormal regions except for ground–glass opacity and a narrower pulmonary blood vessel volume. A negative correlation was found between abnormal areas with lower Hounsfield units (HU) than the normal lung and the ratio of forced expiratory volume in 1 s/forced vital capacity, with narrowed pulmonary blood vessel volume which is positively correlated with abnormal areas with upper HU than the normal lung.Conclusion: This study provided valuable insight into pneumoconiosis progression through a comparison of quantitative CT images based on severity. Furthermore, as there has been paucity of studies on the pulmonary blood vessel volume of the CWP, in this study, a correlation between reduced pulmonary blood vessel volume and regions with low HU values holds significant importance.

Patterns and Implications of Intracranial Atherosclerosis in Anterior and Posterior Circulation Identified by High-Resolution Vessel Wall Imaging

Introduction: Anterior and posterior circulation atheroscleroses differ in vascular risk factors and stroke patterns. Posterior circulation stroke has worse clinical outcomes. However, few studies described the differentiation of plaque features between anterior and posterior circulation atheroscleroses via high-resolution vessel wall imaging (HR-VWI). We aimed to compare the plaque imaging features between anterior and posterior circulations to highlight the relevance of plaque imaging features to clinical events of ischemic stroke. Methods: Prospective data from a HR-VWI cohort of adult patients with acute ischemic stroke or transient ischemic attack were retrospectively analyzed. Quantitative and qualitative measurements of atherosclerotic plaques along the middle cerebral arteries (MCAs), the basilar artery (BA), and the vertebral arteries (VAs) were conducted on HR-VWI. Vessels with stenotic degrees over 30% were identified on the matched time-of-flight magnetic resonance angiography (TOF-MRA) and visually classified into normal, irregular, stenotic, and occluded. The sensitivity, specificity, positive and negative predictive values for TOF-MRA in detecting abnormal vessels were calculated by using quantification on the basis of HR-VWI findings as the reference standard. Results: One hundred and one patients (median age, 64 years old; 62.4% males) were included in this study. A total of 292 plaques were identified, with 152 in the MCAs, 35 in the BA, and 105 in the VAs. The VAs possessed significantly higher enhancement index (EI) (median 38.37 vs. 18.40, p <0.001), more plaques with positive remodeling (76.2% vs. 57.2%, p = 0.002) and intraplaque hypo-intensity (43.8% vs. 12.5%, p <0.001) than the MCAs. The MCAs presented with more intraplaque hemorrhage (IPH) (20.4% vs. 8.6%, p = 0.014) than the VAs. The sensitivity and specificity of TOF-MRA for evaluating luminal stenosis were 89.0 (82.5–93.4) and 66.7 (24.1–94.0) in anterior circulation, respectively, and were 75.2 (66.7–82.2) and 27.3 (7.3–60.7) in posterior circulation, respectively. Conclusion: Our findings might elucidate the clinical events and outcomes in anterior and posterior circulation stroke. Posterior circulation atherosclerosis had higher EI and more plaques with hypo-intensity, suggesting a heavier atherosclerosis burden. Positive remodeling pattern in posterior circulation atherosclerosis might create an impression of “wider” vascular lumen, leading to possible underestimation of atherosclerosis burden of posterior circulation on TOF-MRA as compared to HR-VWI. Besides, anterior circulation atherosclerosis with IPH might be associated with plaque rupture and artery-to-artery embolism. Future studies are needed to verify these findings.