Development Of Restenosis Research Articles

Drug-coated balloon therapy is more effective in treating late drug-eluting stent in-stent restenosis than the early occurring one-a systematic review and meta-analysis.

Drug-eluting stent in-stent restenosis (DES-ISR) remains one of the important assignments to be resolved in interventional cardiology, as it is present in 5%-10% of total percutaneous coronary intervention cases. Drug-coated balloon (DCB) utilization is promising, as it comes with long-term protection from recurrent restenosis in optimal conditions without the hazard of higher risk for stent thrombosis and in-stent restenosis. We aim to reduce the need for recurrent revascularization in DES-ISR, specifying the population in which the DCB therapy should be used. In this meta-analysis, the results of studies containing data on the time frame between drug-eluting stent implantation and the clinical presentation of in-stent restenosis and concomitant drug-coated balloon treatment were summarized. A systematic search was performed in Medline, Central, Web of Science, Scopus and Embase databases on November 11th, 2021. The QUIPS tool was used to assess the risk of bias in the included studies. The occurrence of a major cardiac adverse events (MACE) composite endpoint, containing target lesion revascularization (TLR), myocardial infarction, and cardiac death, and each of these separately, was assessed at 12 months after the balloon treatment. Random effects meta-analysis models were used for statistical analysis. Data of 882 patients from four studies were analyzed. Across the included studies, a 1.68 OR (CI 1.57-1.80, p < 0.01) for MACE and a 1.69 OR (CI 1.18-2.42 p < 0.01) for TLR were observed, both in favor of late DES-ISR. The main limitation of the study is the relatively low patient number. Nevertheless, this analysis shows the first statistically significant results for the effect of DCB treatment in the early or late presentation of DES-ISR. As to date, intravascular imaging (IVI) remains limitedly accessible, other landmarks as the time frame of in-stent restenosis development are to be pursued to advance therapeutic outcomes. In consideration of other biological, technical and mechanical factors, time frame of occurrence as a prognostic factor could reduce the burden of recurrent revascularization in patients at an already high risk. Systematic Review Registration: identifier [CRD42021286262].

Serum Nuclear Factor Erythroid-2 Related Factor-2 (NRF2) as an Indicator of Oxidative Stress is Related to Coronary in-Stent Restenosis

Objective: In the treatment of coronary artery disease, stent implantation has become the standard treatment, but development of in-stent restenosis (ISR) limits the benefit of this treatment modality. Methods: Based on the connection between oxidative stress and thiol/disulphate and NRF2, it was intended to measure NRF2 and thiol/disulphate levels. Results: Coronary angiography images of 76 stable angina pectoris patients were evaluated. Of the 51 patients with a history drug eluting stent implantation, we determined 25 patients with ISR (Group 1) and 26 patients without ISR (Group 2). Twenty-five patients with normal coronary arteries were included in the study as control group (Group 3). NRF2 level was found to be significantly higher in patients who did not develop ISR (p=0.01). Total thiol was significantly higher in group 3 (738.76 micromole/L) compared to group 1 (626.11 micromole/L) and group 2 (630.27 micromole/L) (p=0.014). Native thiol was also significantly higher in group 3 (570.53 micromole/L) compared to group 1 (483.91 micromole/L) and group 2 (501 micromole/L) (p=0.006). Conclusion: We think that total and native thiol levels might be useful as an indicator of oxidative stress in early diagnosis of coronary artery disease, and the NRF2 level can be used in predicting patients who might develop coronary ISR.

Markers of Restenosis after Percutaneous Transluminal Balloon Angioplasty in Patients with Critical Limb Ischemia.

Among cardiovascular diseases, chronic obliterating lesions of the arteries of lower extremities, which are one of the important problems of modern healthcare, are distinguished. In most cases, the cause of damage to the arteries of lower extremities is atherosclerosis. The most severe form is chronic ischemia, characterized by pain at rest and ischemic ulcers, ultimately increasing the risk of limb loss and cardiovascular mortality. Therefore, patients with critical limb ischemia need limb revascularization. Percutaneous transluminal balloon angioplasty is one of the least invasive and safe approaches, with advantages for patients with comorbidities. However, after this procedure, restenosis is still possible. Early detection of changes in the composition of some molecules as markers of restenosis will help screen patients at the risk of restenosis, as well as find ways to apply efforts for further directions of inhibition of this process. The purpose of this review is to provide the most important and up-to-date information on the mechanisms of restenosis development, as well as possible predictors of their occurrence. The information collected in this publication may be useful in predicting outcomes after surgical treatment and will also find new ways for the target implication to the mechanisms of development of restenosis and atherosclerosis.

Development of PR Restenosis after Percutaneous Balloon Pulmonary Valvuloplasty

Background: Pulmonary stenosis is not an uncommon congenital heart disease in our population. Various age groups present with severe pulmonary stenosis require intervention either surgical or percutaneous catheter-based. Often lifesaving surgical intervention is not feasible considering procedural risk, the patient’s physical condition, and young age. Percutaneous balloon pulmonary valvuloplasty is safe, effective, almost painless, economical, and less hospital stay in any age group with immediate and long-term success. This study aimed to analyze the rate of development of (Pulmonary Regurgitation) PR restenosis after Percutaneous Balloon Pulmonary Valvuloplasty (PBPV). Material Methods: This hospital-based prospective observational study was conducted in the Department of Paediatric Cardiology Combined Military Hospital (CMH), Dhaka from January to December 2021. 0-18 years aged 50 population with PS who were referred to the Paediatric Cardiology Department of CMH Dhaka during the study period were selected as study subjects as per inclusion criteria. The purposive Sampling technique was used in this study. Data were collected with a predesigned standard data collection sheet. Statistical significance was set as a 95% confidence level at a 5% acceptable error level. Categorical variables were expressed as frequency and percentages. Mean, standard deviation, and/or medians with interquartile ranges were used to express the continuous variables. Paired t-test was performed in categorical comparison. A p-value of &lt;0.05 was considered statistically significant. Collected data were analyzed using SPSS Version 24. Written informed consent was taken from every parent. Ethical clearance was taken from the Ethics Review Committee of CMH Dhaka for conducting the study. Results: 50(6.39%) had isolated valvular PS. The international standard for the prevalence of isolated PS is 8-10% which is very close to this study’s result. In this study, male predominance was found with the male-female ratio of 3:2 though there was no gender dominance found in other studies. Out of 50 cases, 3(6%) are neonates,7(14%) are infants, 27 (54%) are 1-5 years aged, and 13(26%) are more than 5 years aged. A total of 13(26%) cases developed PR, and all 13 patients developed trivial PR on D1 echo, out of them 1 patient developed mild PR on D30 Echo but in D90 and D180 Echo patients persisted the same mild PR. Out of 50 cases, 46(92%) were successful and 4 cases were procedure failed. None of the successful cases developed restenosis. Out of 4 procedure failed cases 1 patient developed restenosis on D30 follow up and 2 patients develop restenosis on the D90 follow-up. At D180 follow up none of the patients developed restenosis. All the restenosis cases had dysplastic pulmonary valves. One patient’s PS gradient persisted at 30-50 mm of Hg throughout the follow-up period. Overall restenosis in 180-day follow-up is 3(6%) and the remaining 47(94%) cases lead a healthy life in 6 months follow-up. Reballooning was done immediately after diagnosis of restenosis in stenosed cases. Conclusion: Immediate and intermediate-term (6 months) follow-up with Doppler echocardiography showed excellent outcomes in all cases except 3 (6.0%) restenosis cases and 13 (26.0%) insignificant PR cases. The baby who all had restenosis, had the risk factor, like- dysplastic PV. It may be concluded that balloon valvuloplasty is the procedure of choice for moderate, severe, and critical pulmonary valve stenosis.

Causes and risk factors for stent restenosis in patients after percutaneous coronary interventions

Percutaneous coronary intervention (PCI) is one of the main components in the treatment of the coronary artery disease (CAD) and especially its acute forms. Nevertheless, restenosis of stented coronary arteries, which significantly worsens the course of CAD, remains a significant clinical problem of this technology. Prevention of this complication requires a modern understanding of the complex pathogenetic mechanisms of restenosis. Based on the literature data, the frequency of restenosis development in stents with medical coatings is in the range from 3 to 20 %. The mechanism of restenosis is multifactorial and includes biological, mechanical, and genetic factors. The main mechanical causes are insufficient expansion of the stent or its destruction, and biological factors include local inflammation, leading to aggressive neointimal proliferation and late neoatherosclerosis. The search for genetic factors and possibilities of influence on the development of this complication is still ongoing. Intracoronary imaging is crucial for identifying mechanisms of restenosis and selecting individual therapy.

Acute injury to the mouse carotid artery provokes a distinct healing response.

Treatment of vascular stenosis with angioplasty results in acute vascular damage, which may lead to restenosis. Owing to the highly complex cellularity of blood vessels, the healing response following this damage is incompletely understood. To gain further insight into this process, scRNA-seq of mouse carotid tissue after wire injury was performed. Stages of acute inflammation, resolution and remodeling were recapitulated in these data. To identify cell types which give rise to neointima, analyses focused on smooth muscle cell and fibroblast populations, and included data integration with scRNA-seq data from myocardial infarction and atherosclerosis datasets. Following carotid injury, a subpopulation of smooth muscle cells which also arises during atherosclerosis and myocardial infarction was identified. So-called stem cell/endothelial cell/monocyte (SEM) cells are candidates for repopulating injured vessels, and were amongst the most proliferative cell clusters following wire-injury of the carotid artery. Importantly, SEM cells exhibit specific transcriptional profiles which could be therapeutically targeted. SEM cell gene expression patterns could also be detected in bulk RNA-sequencing of neointimal tissue isolated from injured carotid vessels by laser capture microdissection. These data indicate that phenotypic plasticity of smooth muscle cells is highly important to the progression of lumen loss following acute carotid injury. Interference with SEM cell formation could be an innovative approach to combat development of restenosis.

Иммунный статус в развитии рестеноза у пациентов с окклюзионно-стенотическим поражением бедренно-подколенного артериального сегмента после бедренно-подколенного шунтирования

Objective: to assess the immune status of systemic and local blood flow after femoral-popliteal bypass surgery in patients with and without restenosis. Materials and methods. The analysis of the treatment of 82 patients who underwent femoral-popliteal bypass surgery was carried out. Depending on the condition of the reconstruction zone after 12 months, the patients were divided into two groups: group I - 21 patients without restenosis, group II - 61 patients with the development of restenosis. The analysis of IgA, IgM, IgG, circulating immune complexes (CIC), interleukin (IL)-6, IL-1 in the systemic and local blood flow before and after surgery was performed. Results. In patients with the development of restenosis of the reconstruction zone, the level of IgA in the systemic and IgA, IgM in the local bloodstream was initially lower, the level of CIC, IL-1, IL-6 in the systemic and IgG, IL-1, IL-6 in the local bloodstream was higher, after surgery, the level of IgA in the local bloodstream was lower, higher - IgM in systemic and IL-6 in local blood flow in comparison with patients without restenosis. The correlation between the immune status and the development of restenosis was established: before surgery in the systemic circulation - IgA (r=-0.31, p&lt;0.01), CIC (r=0.39, p&lt;0.001), IL-6 (r=0.25, p&lt;0.05), IL-1 (r=0.26, p&lt;0.05), in the local bloodstream - IgA (r=-0.26, p&lt;0.05), IgM (r=-0.30, p&lt;0.01), IgG (r=0.26, p&lt;0.05), IL-6 (r=0.30, p&lt;0.01), IL-1 (r=0.29, p&lt;0.01); after surgery in the systemic circulation - IgM (r=0.33, p&lt;0.01), in the local - IgA (r=-0.24, p&lt;0.05), IL-6 (r=0.40, p&lt;0.001). The relationship between the degree of chronic arterial insufficiency (r=0.22, p&lt;0.05), the ankle- brachial index after surgery (r=-0.27, p&lt;0.05) with the development of restenosis was revealed. Conclusion. The interrelation of the immune status of the systemic and local blood flow before and after surgery and restenosis in the anastomosis zone after femur-popliteal bypass surgery has been shown. The study of the immune status will make it possible to develop an algorithm for restenosis prevention.

ФУНКЦИОНАЛЬНАЯ АКТИВНОСТЬ ЭНДОТЕЛИЯ В СИСТЕМНОМ И МЕСТНОМ КРОВОТОКЕ У ПАЦИЕНТОВ ОБЛИТЕРИРУЮЩИМ АТЕРОСКЛЕРОЗОМ И РАЗВИТИЕ РЕСТЕНОЗА ПОСЛЕ ОПЕРАЦИИ БЕДРЕННО-ПОДКОЛЕННОГО ШУНТИРОВАНИЯ

Objective: To analyze the role of markers of the endothelial dysfunction in the vessels of the systemic and local blood flow before and after femoropopliteal bypass surgery (FPBS) in the development of restenosis at obliterating lesions of the femoropopliteal arterial segment (FPAS). Methods: The results of the examination and treatment of 82 patients with obliterating atherosclerosis who underwent FPBS were analyzed. Before and after surgery they underwent testing for serum homocysteine, oxidized low-density lipoprotein, soluble vascular cell adhesion molecule-1 (sVCAM-1), plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (t-PA), and annexin V in the systemic and local blood flow. Based on the condition of the reconstruction zone after 12 months, all patients were divided into two groups. Group 1 included patients without restenosis (n=21), and Group 2 – with restenosis (n=61). Results: Before surgery Group 2 patients showed significant differences in the severity of adhesive and hemostatic forms of endothelial dysfunction, as well as apoptosis in comparison with Group 1. It was found that before surgery, Group 2 patients had a significantly higher level of sVCAM-1 in the local bloodstream (by 37.5%, p=0.014), PAI-1 in the systemic and local bloodstream (by 15.6%, p=0.010, and by 16.4%, p=0.008 respectively) and annexin V in the systemic and local bloodstream (by 48.9%, p=0.012 and by 60.2%, p=0.002 respectively). After surgery Group 2 patients had significantly higher levels of PAI-1 in the systemic (by 18.9%, p=0.004) and local (by 11.1%, p=0.049) blood flow, and annexin V in the systemic circulation (by 28.4%, p=0.011) compared with Group 1. Thus increased levels of sVCAM-1 in the local bloodstream, PAI-1, and annexin V – in the systemic and local bloodstream before surgery were associated with postoperative development of restenosis, while higher values of PAI-1 in the systemic and local bloodstream and annexin V in the systemic circulation after surgery were related to subsequent restenosis development. Conclusion: The results of the study indicate impairment of the adhesive and hemostatic function of the endothelium, and increased level of apoptosis in the blood vessels of systemic and local blood flow in patients with restenosis, which can be used to develop personalized approach to management of this disorder and improve the results of revascularization interventions on FPAS. Keywords: Obliterating atherosclerosis of the lower extremities, femoropopliteal bypass surgery, functional activity of the endothelium, restenosis.

The role of increased serum creatinine level in adverse outcomes of endovascular revascularisation in patients with acute coronary syndrome

Ischemic kidney damage as part of acute coronary syn-drome (ACS) largely contributes to the development of un-favorable outcomes not only of the underlying disease, but also of endovascular procedures, aggravating the patient’s condition and prognosis. This study is aimed at assessing the long-term results of coronary stenting for ACS in pa-tients with a sharp increase in serum creatinine levels wit-hin 48 hours after the intervention. Purpose: to evaluate the relationship between an increase in serum creatinine levels after coronary stenting of an infarct-related artery and the development of adverse outcomes in the long term. Materials and methods: 51 patients with ACS took part in the study. Serum creatinine was assessed before and wit hin 48 hours after coronary stenting. Subsequent-ly, after 3–6 months, patients underwent repeat coronary angiography to assess the patency of the coronary bed. Results: based on repeated coronary angiography, we identified the development of angiographic restenosis in those patients who demonstrated a significant increase in serum creatinine levels within 48 hours after stent implan-tation. In the group of patients without restenosis, creati-nine values before and after revascularization were com-parable. Conclusion: we noted that kidney damage due to acute coronary syndrome in combination with the intro-duction of a large volume of contrast agent can contribute to the development of unfavorable outcomes of coronary sten ting in the long term, namely, in-stent restenosis

Влияние применения комбинированной антиоксидантной терапии на результаты эндоваскулярного лечения пациентов с облитерирующим атеросклерозом артерий нижних конечностей

INTRODUCTION: The number of endovascular interventions performed on the arteries of the lower extremities is growing annually in the world, as they provide faster patient recovery and shorten the period of hospital stay. However, the development of restenosis of the reconstruction zone often leads to a need for repeated operations. AIM: To evaluate the effectiveness of combined antioxidant therapy in reducing the risk of restenosis after endovascular interventions. MATERIALS AND METHODS: The study included 84 patients with IIB–III stage peripheral arterial disease (PAD). Group A included 45 patients who underwent endovascular interventions, group B included 39 patients who were prescribed combined antioxidant therapy (Vitamin E, Actovegin®) a week before endovascular intervention and within a week after. On admission to hospital, in the first hours of stay, in 1, 7 days after surgery, the amount of Bax and platelet growth factor (PDGF BB) biomarkers were determined in the blood serum of all the patients. On control visits, the patients underwent duplex scanning of the arteries of the lower extremities to measure the thickness of the neointima and to detect restenosis of the intervention area. RESULTS: When comparing Bax values in the first hours and days after surgery in groups A and B, its growth was noted in patients of the first group (p &lt; 0.01). At the same time, in patients of group A, the increase in PDGF BB was more pronounced (p &lt; 0.01) on the 7th day. In patients of group A with restenosis of the reconstruction zone, the values of Bax marker in the first hours after surgery exceeded those in patients of group B (р &lt; 0.01). On the 7th day, the amount of PDGF BB in these patients of group A was increased relative to group B (р &lt; 0.01). The changes in the number and dynamics of the studied markers in group B patients with restenosis of the reconstruction zone led, firstly, to decrease in the percentage of stenosis in the area of the previous surgical intervention, secondly, to decrease in the severity of the clinical manifestation of this complication, thirdly, to occurrence of restenosis of the reconstruction zone in the later period, and, fourthly, to decrease in the percentage of patients with this complication. CONCLUSION: The use of combined antioxidant therapy targeted at the system of apoptosis, can reduce the thickness of the neointima of the reconstruction zone and reduce the percentage of patients with restenosis after endovascular interventions.

Noncoding RNAs in Vascular Cell Biology and Restenosis.

In-stent restenosis (ISR), characterised by ≥50% re-narrowing of the target vessel, is a common complication following stent implantation and remains a significant challenge to the long-term success of angioplasty procedures. Considering the global burden of cardiovascular diseases, improving angioplasty patient outcomes remains a key priority. Noncoding RNAs (ncRNAs) including microRNA (miRNA), long noncoding RNA (lncRNA) and circular RNA (circRNA) have been extensively implicated in vascular cell biology and ISR through multiple, both distinct and overlapping, mechanisms. Vascular smooth muscle cells, endothelial cells and macrophages constitute the main cell types involved in the multifactorial pathophysiology of ISR. The identification of critical regulators exemplified by ncRNAs in all these cell types and processes makes them an exciting therapeutic target in the field of restenosis. In this review, we will comprehensively explore the potential functions and underlying molecular mechanisms of ncRNAs in vascular cell biology in the context of restenosis, with an in-depth focus on vascular cell dysfunction during restenosis development and progression. We will also discuss the diagnostic biomarker and therapeutic target potential of ncRNAs in ISR. Finally, we will discuss the current shortcomings, challenges, and perspectives toward the clinical application of ncRNAs.

The critical period for development of secondary restenosis following post-intubation tracheal stenosis surgery

Background Determining a predictable duration to restenosis very essential for reducing mortality and morbidity for tracheal stenosis surgery. Objectives The aim of this study was to determine the critical periods for secondary restenosis risk for operated patients with post-intubation tracheal stenosis (PITS) during the initial healing period. Methods A total of 61 patients with a diagnosis of surgically treated PITS were included in the study. Treatment groups were carbon dioxide (CO2) laser and tracheal resection with primary anastomosis (TRPA). Duration to restenosis was compared with Kaplan–Meier curves between study groups. Results Restenosis developed in 11 (18.0%) patients and was diagnosed after a mean of 39.3 ± 38.5 (range, 22 to 155) days. Gender or Cotton–Myer grade of the PITS was not found to be risk factors for the development of stenosis. Restenosis rate was 33.3% in CO2 laser group and 10% in the TRPA group (p = .036). Duration to restenosis was detected at a median of 28 days in patients treated with CO2 laser, and a median of 30 days in patients treated with TRPA (p = .024). Conclusions The most critical period for the development of restenosis after PITS treatment is the third and fourth weeks, especially in patients treated with CO2 laser.

Effect of balloon pre-dilation on performance of self-expandable nitinol stent in femoropopliteal artery

Balloon pre-dilation is usually performed before implantation of a nitinol stent in a femoropopliteal artery in a case of severe blockage or calcified plaque. However, its effect on performance of the nitinol stent in a diseased femoropopliteal artery has not been studied yet. This study compares the outcomes of stenting with pre-dilation and without it by modelling the entire processes of stent deployment. Fatigue deformation of the implanted stent is also modelled under diastolic–systolic blood pressure, repetitive bending, torsion, axial compression and their combination. Reduced level of stress in the stent occurs after stenting with pre-dilation, but causing the increased damage in the media layer, i.e. the middle layer of the arterial wall. Generally, pre-dilation increases the risk of nitinol stent’s fatigue failure. Additionally, the development of in-stent restenosis is predicted based on the stenting-induced tissue damage in the media layer, and no severe mechanical irritation is induced to the media layer by pre-dilation, stent deployment or fatigue loading.

Serum glycated albumin is associated with in-stent restenosis in patients with acute coronary syndrome after percutaneous coronary intervention with drug-eluting stents: An observational study.

BackgroundPrevious studies have confirmed the predicted value of serum glycated albumin (GA) in atherosclerotic cardiovascular disease. However, the relationship between GA and the development of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation has not been verified in patients with acute coronary syndrome (ACS).Materials and methodsIn this study, 797 patients diagnosed with ACS who underwent re-coronary angiography more than 6 months after the first successful DES-based percutaneous coronary intervention (PCI) were eventually included. Patients were categorized into two groups based on the median GA levels of 14.94%. Moreover, multivariate logistic regression analysis models and the net reclassification improvement and integrated differentiation improvement risk models were constructed to assess the relationship between the GA and DES-ISR in patients with ACS.ResultsThe GA was significantly associated with an increased risk of DES-ISR, upon adjusting for confounding factors (as nominal variate: OR 1.868, 95% CI 1.191–2.932, P = 0.007; as continuous variate: OR 1.109, 95% CI 1.040–1.183, P = 0.002). The addition of GA to a baseline risk model had an incremental effect on the predictive value for DES-ISR (AUC: GA vs. baseline model, 0.714 vs. 0.692, comparison P = 0.017; category-free net reclassification improvement (NRI) 0.080, P = 0.035; integrated discrimination improvement (IDI) 0.023, P < 0.001).ConclusionGA level was significantly associated with a high risk of DES-ISR in patients with ACS treated with PCI. Moreover, the addition of the GA to a baseline risk model has an incremental effect on the predictive potential for DES-ISR.

Tailoring surface properties, biocompatibility and corrosion behavior of stainless steel by laser induced periodic surface treatment towards developing biomimetic stents

Laser-Induced Periodic Surface Structures (LIPSS) holds great potential for regenerative biomedicine. Creating highly precise LIPSS enables to generate biomimetic implant surfaces with improved properties. The present study focuses on the fabrication and investigation of laser-treated stainless steel samples with applied linear LIPSS patterns with grooves made by means of a picosecond laser system using wavelengths of 1064 nm and 532 nm. To investigate properties of the laser-treated surfaces and to understand the basics of cell-surface interactions between the LIPSS and human Umbilical Cord Mesenchymal Stem Cells (UCMSC), flat stainless steel samples with various applied nanopatterns were used. Such LIPSSs demonstrated higher surface roughness, good biocompatibility, lower wettability and higher corrosion resistance compared to the untreated (polished) specimens. The surface roughness of laser-treated samples was in microscale that enabled adhesion and migration of endothelial cells, thus increasing the likelihood for endothelialisation. This thereby could reduce the chances for the development of Late Stent Thrombosis (LST) and In-Stent Restenosis (ISR). Furthermore, laser textured surfaces demonstrated an environment supportive for cell attachment, proliferation and alignment with the nanogroves. Therefore, application of the biomimetic nanopatterns could help to overcome frequent post-surgery complications after the stent implantation.

An intricate interplay between stent drug dose and release rate dictates arterial restenosis.

Since the introduction of percutaneous coronary intervention (PCI) for the treatment of obstructive coronary artery disease (CAD), patient outcomes have progressively improved. Drug eluting stents (DES) that employ anti-proliferative drugs to limit excess tissue growth following stent deployment have proved revolutionary. However, restenosis and a need for repeat revascularisation still occurs after DES use. Over the last few years, computational models have emerged that detail restenosis following the deployment of a bare metal stent (BMS), focusing primarily on contributions from mechanics and fluid dynamics. However, none of the existing models adequately account for spatiotemporal delivery of drug and the influence of this on the cellular processes that drive restenosis. In an attempt to fill this void, a novel continuum restenosis model coupled with spatiotemporal drug delivery is presented. Our results indicate that the severity and time-course of restenosis is critically dependent on the drug delivery strategy. Specifically, we uncover an intricate interplay between initial drug loading, drug release rate and restenosis, indicating that it is not sufficient to simply ramp-up the drug dose or prolong the time course of drug release to improve stent efficacy. Our model also shows that the level of stent over-expansion and stent design features, such as inter-strut spacing and strut thickness, influence restenosis development, in agreement with trends observed in experimental and clinical studies. Moreover, other critical aspects of the model which dictate restenosis, including the drug binding site density are investigated, where comparisons are made between approaches which assume this to be either constant or proportional to the number of smooth muscle cells (SMCs). Taken together, our results highlight the necessity of incorporating these aspects of drug delivery in the pursuit of optimal DES design.

Hematoporphyrin- mediated focused ultrasound sonodynamic therapy combined with catheter- based rhenium-186 brachytherapy after B- mode ultrasound- guided balloon angioplasty of occluded artery

Background and Aims : Three mechanisms are responsible for the development of restenosis: elastic recoil, intimal hyperplasia and late vascular constriction, all grouped under the catch phrase “negative remodeling”. Neointimal hyperplasia is usually defined in an artery as thickening of the intimal layer after an injury such as balloon angioplasty methods. The aim of this study was to evaluate the effect of combined ultrasound sonodynamic therapy and catheter- based 186Re-mediated beta radiation (β-) brachytherapy on restenosis reduction after balloon angioplasty.

Design and Verification of a Novel Perfusion Bioreactor to Evaluate the Performance of a Self-Expanding Stent for Peripheral Artery Applications.

Endovascular stenting presents a promising approach to treat peripheral artery stenosis. However, a significant proportion of patients require secondary interventions due to complications such as in-stent restenosis and late stent thrombosis. Clinical failure of stents is not only attributed to patient factors but also on endothelial cell (EC) injury response, stent deployment techniques, and stent design. Three-dimensional in vitro bioreactor systems provide a valuable testbed for endovascular device assessment in a controlled environment replicating hemodynamic flow conditions found in vivo. To date, very few studies have verified the design of bioreactors based on applied flow conditions and their impact on wall shear stress, which plays a key role in the development of vascular pathologies. In this study, we develop a computationally informed bioreactor capable of capturing responses of human umbilical vein endothelial cells seeded on silicone tubes subjected to hemodynamic flow conditions and deployment of a self-expanding nitinol stents. Verification of bioreactor design through computational fluid dynamics analysis confirmed the application of pulsatile flow with minimum oscillations. EC responses based on morphology, nitric oxide (NO) release, metabolic activity, and cell count on day 1 and day 4 verified the presence of hemodynamic flow conditions. For the first time, it is also demonstrated that the designed bioreactor is capable of capturing EC responses to stent deployment beyond a 24-hour period with this testbed. A temporal investigation of EC responses to stent implantation from day 1 to day 4 showed significantly lower metabolic activity, EC proliferation, no significant changes to NO levels and EC's aligning locally to edges of stent struts, and random orientation in between the struts. These EC responses were indicative of stent-induced disturbances to local hemodynamics and sustained EC injury response contributing to neointimal growth and development of in-stent restenosis. This study presents a novel computationally informed 3D in vitro testbed to evaluate stent performance in presence of hemodynamic flow conditions found in native peripheral arteries and could help to bridge the gap between the current capabilities of 2D in vitro cell culture models and expensive pre-clinical in vivo models.

Physical Characteristics and Cellular Pharmacological Activity of Baicalin-Lecithin Complex-Loaded Poly(lactic-co-glycolic acid) Membranes

In this study, the physiochemical properties and cellular-level biological effects of baicalin-lecithin complex (BLC)-loaded poly(lactic-co-glycolic acid) (PLGA) membranes were studied. Several parameters were measured to evaluate the preparation of these membranes, such as the coating thickness, scanning electron microscopy-detected surface morphology, X-ray diffraction, Fourier transform infrared spectroscopy, and thermodynamic behavior. The drug-release behavior was mainly controlled by the degradation of the PLGA. The release of BLC lasted for more than one month, which matched the development of the restenosis process. The BLC-coated PLGA (60:40) membrane had good drug release in terms of its long release cycle, and the efficacy of baicalin in the form of BLC in cardiovascular stents matched the development of restenosis. In vitro cell culture test showed that endothelial cells (ECs) and smooth muscle cells (SMCs) for 12 h, 1 d and 3 d, BLC-loaded PLGA membranes (1%, 5% and 10% (w/w)) had significant activity towards the proliferation of ECs and the inhibition of SMC proliferation (P &lt; 0.05). BLC-loaded PLGA film has good drug release trends.

Relationship Between Neutrophil-Lymphocyte Ratio and Drug-Coated Balloon Restenosis in Patients With Femoropopliteal Arterial Disease.

We investigated the relationship between neutrophil-lymphocyte ratio (NLR) and restenosis in patients with femoropopliteal arterial disease following drug-coated balloon (DCB) angioplasty. Patients (n = 120) were divided into 3 groups according to the development of restenosis and the time of restenosis occurrence. The postoperative NLR was higher in the late-restenosis group than that in the no-restenosis group (3.53 vs 2.70; p = .011). In multivariate logistic analysis, postoperative NLR was an independent predictor of late restenosis (odds ratio: 1.404, 95% confidence interval: 1.073-1.839; p = .014). The postoperative NLR cutoff value for predicting late restenosis was 2.78 with a sensitivity of 80.8% and a specificity of 53.2% (area under the ROC curve was .666 (95% CI: .541-.791, p = .010). The incidence of late restenosis in the NLR ≥2.78 group was higher than that in the NLR <2.78 group (32.3 vs 9.1%; p = .002). Postoperative NLR is independently associated with late restenosis in patients treated with DCB for femoropopliteal arterial disease.