UNASSIGNED: Neoatherosclerosis (NA) is associated with stent failure. However, systematic studies on the manifestations of NA and neovascularization (NV) at different stages after drug-eluting stent (DES) implantation are lacking. Moreover, the relationship between NA and NV in in-stent restenosis (ISR) has not been reported. This study aimed to characterize NA and NV in patients with ISR at different post-DES stages and compare the association between NA and NV in ISR lesions.
UNASSIGNED: A total of 227 patients with 227 lesions who underwent follow-up optical coherence tomography before percutaneous coronary intervention for DES ISR were enrolled and divided into early (E-ISR: < 1 year), late (L-ISR: 1-5 years), and very-late (VL-ISR: > 5 years) ISR groups. Furthermore, ISR lesions were divided into NV and non-NV groups according to the presence of NV.
UNASSIGNED: The prevalence of NA and NV was 52.9% and 41.0%, respectively. The prevalence of lipidic NA (E-ISR, 32.7%; L-ISR, 50.0%; VL-ISR, 58.5%) and intimal NV (E-ISR, 14.5%; L-ISR, 30.8%; VL-ISR, 38.3%) increased with time after stenting. NA was higher in ISR patients with NV lesions than in those without (p < 0.001). Patients with both ISR and NV had a higher incidence of macrophage infiltration, thin-cap fibroatheroma, intimal rupture, and thrombosis (p < 0.01).
UNASSIGNED: Progression of lipidic NA was associated with L-ISR and VL-ISR but may not be related to calcified NA. NA was more common in ISR lesions with NV; its formation may substantially promote NA progression and plaque instability.

Four human acellular dermal matrices (hADMs) were characterized in a nonhuman primate abdominal wall repair model by evaluating host immune response, vascularization, and incorporation into host tissues. AlloDerm™ (electron beam-sterilized hADM [e-hADM]), AlloMax™ (gamma beam-sterilized hADM, freeze-dried [g-hADM-FD]), DermaMatrix™ (hADM, freeze-dried [hADM-FD]), and FlexHD™ (ethanol-treated hADM [EtOH-hADM]) were each implanted in an abdominal wall-bridging defect in nonhuman primates (n = 3 animals/time point, n = 36 animals). Immunohistochemical and histological assessments were conducted on biopsies from each hADM at 1-, 3-, and 6-months postimplantation to assess vascularization (hematoxylin and eosin [H&E], CD31, alpha smooth muscle actin [αSMA], collagen IV), inflammatory/immune response (H&E, CD3, CD20, CD68), and collagen turnover (H&E, matrix metalloproteinase-9 [MMP-9]). MMP-9 immunolabeling was similar among different hADMs at 1 month; however, hADM-FD and EtOH-hADM showed higher total mean MMP-9-immunopositive areas at approximately 16% compared with <1% for e-hADM and g-hADM at 6 months postimplantation. Cells that stained positively for CD68, CD3, and CD20 were generally higher for hADM-FD and EtOH-hADM compared with other hADMs. The mean CD31-immunopositive area, CD31 vessel density, CD31 vessel diameter, and collagen IV-immunopositive area increased over time. Among all the hADM types, e-hADM had the highest mean (±standard deviation [SD]) CD31-immunopositive area at 1.54% ± 1.01%, vessel density at 7.86 × 10-5 ± 3.96 × 10-5 vessels/µm2, and collagen IV-immunopositive area at 2.55% ± 0.73% 1-month postimplantation. The pattern of αSMA immunolabeling varied among the hADMs. Histology showed that overall inflammation was mild at 1 month. Overall fibroblast repopulation and collagen remodeling increased over time from 1 to 6 months postimplantation. Fibroblast infiltration was minimal to mild at 1 month, with e-hADM showing the highest mean (±SD) score at 2.00 ± 0.00 compared with other hADMs. Only hADM-FD was not completely replaced by neotissue formation at 6 months postimplantation. All hADMs promoted vascularization, cell infiltration, and incorporation into host tissue, which were associated with acute inflammation and immune responses, within a 6-month period. A trend toward relatively enhanced early vascularization in e-hADM compared with other hADMs was observed. Immunogenic responses among the hADMs in the present study showed a slight distinction toward more quiescent terminally sterilized hADMs (e-hADM, g-hADM-FD) versus aseptically processed hADMs (EtOH-hADM, hADM-FD).

OBJECTIVE: The goal of this phase III, comparative, multicentric, randomized, double-blinded clinical trial was to investigate the superiority of subconjunctival bevacizumab injections versus placebo in the treatment of corneal neovascularization.
METHODS: We included 38 eyes (38 patients) with corneal neovascularization. Twenty patients received bevacizumab and 18 placebos. Patients received 3 monthly injections of either 5mg (0.2mL) bevacizumab or placebo. The main criteria of success was reduction of the surface area of corneal neovascularization after 3months (M3) versus baseline, as measured using semi-automatic analysis of color photographs.
RESULTS: The percentage of neovascularized corneal surface decreased by -8.6%±32.8 with bevacizumab, versus -2.6%±20.8 with placebo (p=0.5284). Four patients were determined to be responders (reduction of more than 30%), 3 in the bevacizumab group and 1 in the placebo group, all with neovascularization of less than 1year duration. When restricting the analysis to neovascularization of less than 1 year duration, the difference approached the threshold for significance (-31.8%±42.4 in the bevacizumab group and -0.9%±23.1 in the placebo group) (p=0.0637), as well as the number of responders (3/6 in the bevacizumab group versus 1/10 in the placebo group) (p=0.1181). No serious adverse event was reported.
CONCLUSIONS: This study shows the efficacy of subconjunctival bevacizumab injection in the reduction of neovascularized corneal surface area versus placebo, but only when the neovascularization has been present less than 1year. Nevertheless, the study did not attain the statistical power to pass the threshold of significance.

BACKGROUND: Good vision highly depends on the transparency of the cornea, which is the \"windscreen\" of the eye. In fact, corneal blindness due to transparency loss is the second most common cause of blindness worldwide, and corneal transplantation is the main cure. Importantly, the cornea is normally avascular but can secondarily be invaded by pathological (blood and lymphatic) vessels due to severe inflammation, and the survival prognosis of a corneal graft mainly depends on the preoperative vascular condition of the recipient\'s cornea. Whereas transplants placed into avascular recipient beds enjoy long-term survival rates of > 90%, survival rates significantly decrease in pathologically pre-vascularized, so-called high-risk recipients, which account for around 10% of all performed transplants in Germany and > 75% in lower and middle-income countries worldwide.
METHODS: This parallel-grouped, open-randomized, multicenter, prospective controlled exploratory investigator-initiated trial (IIT) intends to improve graft survival by preconditioning pathologically vascularized recipient corneas by (lymph)angioregressive treatment before high-risk corneal transplantation. For this purpose, corneal crosslinking (CXL) will be used, which has been shown to potently regress corneal blood and lymphatic vessels. Prior to transplantation, patients will be randomized into 2 groups: (1) CXL (intervention) or (2) no pretreatment (control). CXL will be repeated once if insufficient reduction of corneal neovascularization should be observed. All patients (both groups) will then undergo corneal transplantation. In the intervention group, remaining blood vessels will be additionally regressed using fine needle diathermy (on the day of transplantation). Afterwards, the incidence of graft rejection episodes will be evaluated for 24 months (primary endpoint). Overall graft survival, as well as regression of corneal vessels and/or recurrence, among other factors, will be analyzed (secondary endpoints).
CONCLUSIONS: Based on preclinical and early pilot clinical evidence, we want to test the novel concept of temporary (lymph)angioregressive pretreatment of high-risk eyes by CXL to promote subsequent corneal graft survival. So far, there is no evidence-based approach to reliably improve graft survival in the high-risk corneal transplantation setting available in clinical routine. If successful, this approach will be the first to promote graft survival in high-risk transplants. It will significantly improve vision and quality of life in patients suffering from corneal blindness.
BACKGROUND: ClinicalTrials.gov NCT05870566. Registered on 22 May 2023.

OBJECTIVE: This study aimed to investigate the value of contrast-enhanced ultrasound (CEUS) and superb microvascular imaging (SMI) in evaluating angiogenesis in carotid artery plaques and prognosis in stroke patients.
METHODS: Sixty-one patients with carotid atherosclerotic plaques were selected. All patients received conventional ultrasound, CEUS, and SMI examination, including 32 patients with cerebral infarction and 29 patients without cerebral infarction. The results of CEUS and SMI neovascularization of patients were graded 0, 1, and 2 points according to the image characteristics. The consistency between SMI results and CEUS results was evaluated, and the differences in neovascularization in carotid plaques between patients with cerebral infarction and those without cerebral infarction were compared.
RESULTS: SMI showed that the neovascularization score in plaque was 0 point in 13 cases, 1 point in 24 cases, and 2 points in 24 cases. There were no significant differences in age, sex, plaque size, or echo between the two groups. There was no significant difference between the SMI and CEUS results, P > .05. The CEUS neovascularization grade of patients with cerebral infarction had a higher score, which was significantly different from that of patients without cerebral infarction, P < .05. The SMI neovascularization grade of patients with cerebral infarction had a higher score, which was significantly different from that of patients without cerebral infarction, P < .05.
CONCLUSIONS: SMI can show neovascularization in plaques, with a significantly higher grade of neovascularization in those of patients with cerebral infarction than in those without cerebral infarction.

BACKGROUND: XTEND (NCT03939767) is a multicenter, observational, prospective study of patients with treatment-naïve neovascular age-related macular degeneration (nAMD) in routine clinical practice. The study aims to examine treatment outcomes of proactive intravitreal aflibercept (IVT-AFL) treatment regimens (fixed dosing or treat-and-extend) according to local marketing labels.
METHODS: Study eyes received IVT-AFL injections as per the local label. The mean changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to month (M) 12 and M24 were measured and stratified by baseline factors. Treatment exposure and safety data were evaluated. Statistical analysis was descriptive.
RESULTS: Overall, 1466 patients from 17 countries were treated. For the overall population, the mean ± standard deviation (SD) age was 78.7 ± 8.5 (range 50-100) years, and 891 patients (60.8%) were female. The mean ± SD baseline BCVA was 54.3 ± 20.3 letters and CST was 374 ± 126 µm. At M12 and M24, mean (95% confidence interval [CI]) BCVA change was + 4.3 (3.4, 5.3) and + 2.3 (1.3, 3.3) letters, respectively. Mean (95% CI) CST was - 106 (- 114, - 99) μm and - 109 (- 117, - 102) μm at M12 and M24, respectively. At M24, 41.5% of patients had a BCVA ≥ 70 letters. Patients received a mean ± SD of 7.7 ± 2.7 injections by M12 and 10.8 ± 5.0 injections by M24 (3.1 injections between M12 and M24). Adverse events were consistent with the known safety profile of IVT-AFL.
CONCLUSIONS: The 24-month results indicate that, in routine clinical practice, a proactive IVT-AFL regimen achieves functional improvements in patients with treatment-naïve nAMD. The proportion of patients achieving ≥ 70 letters at M24 increased, and patients with baseline BCVA ≥ 70 letters maintained vision regardless of the followed IVT-AFL label.
BACKGROUND: ClinicalTrials.gov identifier: NCT03939767. A video abstract is available for this article. Supplementary file2 (MP4 364624 KB).

OBJECTIVE: Free gingival graft surgery is the gold standard for increasing the size of keratinized tissue. Blood supply in the recipient site is critical for healing. Therefore, in this study, the effect of FTY720 on angiogenesis, healing, and scar tissue presence following free gingival graft surgery is investigated.
METHODS: Surgeries were performed on 10 New Zealand white rabbits. Rabbits were randomly assigned to two groups. In the experimental group, immediately after surgery, 2 and 4 days later, FTY-720 was injected into the tissue surrounding the recipient site. In the control group, the same frequency of placebo vehicle was injected. After 30 days, tissue samples were assessed histologically and histomorphometrically.
RESULTS: The blood vessel count (P < 0.000) and rete ridge formation (P < 0.05) in the experimental group were significantly higher, while the epithelial thickness was lower in this group (P < 0.000). There was no significant difference in the percentage of regions occupied by collagen fibres between the groups (P = 0.987). Furthermore, a significant and negative relationship between epithelial thickness and blood vessel count was shown (Pearson correlation coefficient =  - 0.917).
CONCLUSIONS: The findings indicate that the angiogenic effects of FTY-720 in the recipient site of free gingival graft can be employed to promote tissue healing and reduce scar tissue presence.
CONCLUSIONS: A significant decrease in epithelial thickness and increase in angiogenesis as well as rete ridge formation score in the FTY-720 group were shown, which can be translated into improved tissue healing and less presence of scar tissue.

The aim of this study is to evaluate the effect on the initiation of new blood vessel formation of rh-BMP-2 administration in the human gingival tissue during bone regeneration surgery.
METHODS: The randomized controlled clinical trial included twenty patients with bilateral partial edentulous of the mandibular premolar and molar region. Each patient received one implants on each side. Only one side received a 0.25 µg injection of rhBMP-2 into the gingival flap and grafted material during guided bone regeneration (GBR) for dental implantation. And the other side received GBR without injection. Three samples were collected from each patient as follows: one from the anterior area of the mandible (control group #1) collected at the time of all implant surgeries, and the two other samples during the placement of healing abutments at 4 months of follow-up, from treated side with rh-BMP-2 (test group) and untreated ones (control group #2). A total of 60 gingival samples were collected. Samples were stained with hematoxylin-eosin, and immunohistochemistry was performed with a vascular endothelial growth factor marker. The number of new vessels in each sample was counted.
RESULTS: Statistical analyses showed a significantly higher number of new vessels in the gingival tissue of the test group.
CONCLUSIONS: Rh-BMP-2 injections into the gingival flap significantly improved new blood vessel formation.

The purpose of this study was to analyze factors affecting good neovascularization after indirect bypass surgery.
From August 2000 to July 2020, postoperative image results and medical records of 132 patients (159 hemispheres) who underwent EDAS of indirect bypass surgery at two institutions were reviewed retrospectively. Based on DSA results, angiogenesis after indirect bypass was divided into \"good\" or \"poor\" according to the Matsushima criteria. STA flap length affecting GPN were analyzed in the entire group (n = 159) and a MMD group (n = 134).
In the entire group, GPN after EDAS was observed in 94 (59.1%) hemispheres. Age, MMD, hypertension, and bone flap size were identified as significant factors in univariate analysis. Also, in the MMD group, 86 (64.2%) hemispheres showed GPN. Hypertension and bone flap size were significant factors in both univariate and multivariate analyses. Cutoff values of bone flap size and GPN were 47.91 cm2 in the entire group and the MMD group.
In all patients who received EDAS, good postoperative neovascularization was significant in those with a young age, MMD, without hypertension, and large bone flap size. No hypertension and large bone flap size were meaningful factors in the MMD group. AUROC showed that an appropriate bone flap size was 47.91 cm2. However, a further controlled prospective study is needed.

The impact of donor transmitted atherosclerosis as assessed by intravascular ultrasound on development and progression of cardiac allograft vasculopathy (CAV) after heart transplantation (HT) remains poorly defined in contemporary practice. In this exploratory analysis, we sought to assess the prognostic role of early qualitative assessment of donor artery morphology using optical coherence tomography (OCT) as a more sensitive imaging modality.
HT recipients were prospectively enrolled for baseline OCT imaging of the left anterior descending coronary artery. OCT findings were classified as normal, homogeneous intimal thickening, and advanced plaque characteristics. The endpoint was a composite of cardiac death, myocardial infarction, or new angiographically detectable CAV stratified by the International Society of Heart and Lung Transplantation criteria up to 4 years of follow-up.
A total of 35 patients underwent baseline OCT of whom 51.4% had normal OCT, 14.3% had homogenous plaque, and 34.3% had advanced characteristics. There were no significant differences in baseline demographics between patients with and without normal morphology. During a mean follow-up of 3.3 ± 0.4 years, the endpoint occurred in 11 patients including 1 death, 7 CAV1, 3 CAV2, and 1 CAV3. Kaplan-Meier analysis revealed a significantly higher event rate in patients with advanced characteristics (log-rank p = 0.010). In multivariate analysis, OCT-based plaque morphology was an independent predictor of clinical events (adjusted hazard ratio 4.57, 95% confidence interval 1.50-13.92, p = 0.008) while maximal intimal thickness ≥0.5 mm was not.
Early qualitative OCT assessment of donor coronary artery morphology appears to be a reliable marker for predicting future cardiovascular events in HT recipients. Our findings warrant more careful study in a larger cohort.