bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microvascular blood flow disturbances predict poor outcome of revascularization in CLTI patients
Authors: Korpisalo P , Frimodig C , Heikkinen H , Happonen K , Tarvainen S , Juusola G , Wirth G 
Published: October 2024

Abstract

Background
We have recently established hypoxic microvascular remodelling as a critical pathomechanistic factor that limits oxygen diffusion to muscle in chronic limb threatening ischaemia (CLTI). Using animal models of experimental hind limb ischaemia we have also displayed the biological relevance of post-ischaemic microvascular remodelling in skeletal muscle. Our results indicate that differential microvascular changes associate to muscle damage and repair. The natural microvascular dynamics that inherently promote muscle recovery are defected in CLTI patients. Particularly, a progressive arterialization of capillaries in CLTI muscle differentiates the dynamics of the microvasculature from initially assisting muscle regeneration to aggravating ischaemic damage.

Methods
To establish the clinical relevance of the post-ischaemic microvascular changes in CLTI, we now have studied the effect of microvascular remodelling on the outcome of CLTI patients undergoing surgical or endovascular revascularization. Contrast enhanced ultrasound was used preoperatively to determine the microvascular status of CLTI patients (n=36) scheduled for immediate revascularization. Outcome events such as: hospitalization; reoperation; leg amputation; or death, were postoperatively followed from medical records up to 6 months after revascularization. Patients were grouped according to muscle capillary transit time (Tct) being either similar (n=18) or shorter (n=18) to that in the contralateral legs of the patients, and treatment outcomes were compared between groups.

Results
The results display consistent increases in postoperative event rates in all measured outcomes in the ShortTct group as compared to controls (at 1 month 8 vs. 2 events (rate ratio 4.00 (95%CI: 0.85-18.84, p=0.080)); at 3 months 13 vs. 4 events (rate ratio 3.25 (95%CI: 1.06-9.97, p=0.039)); at 6 months 17 vs. 9 events (rate ratio 1.89 (95%CI: 0.84-4.24, p=0.123))). For example, 5 vs. 0; 7 vs. 1; and 7 vs. 4 reoperations were detected in the ShortTct group as compared to controls at 1, 3 and 6 months, respectively. By 6 months after initial revascularization also 2 deaths were recorded in the ShortTct group as compared to no deaths in the controls.

Conclusions
Despite still small samples size in this study, these results suggest that microvascular blood flow disturbances, such as short preoperative muscle capillary transit time, can predict poor outcome of CLTI patients after revascularization. Importantly, the results also identify patients with microvascular blood flow disturbances a subgroup of CLTI patients that should likely receive more specialized care to improve outcomes. The results also call for immediate actions from the scientific community to improve clinical detection of microvascular alterations and to develop strategies to normalize microvascular function in CLTI patients.
Evaluation of non-target lesions in femoropopliteal disease using near-infrared spectroscopy intravascular ultrasound imaging
Authors: Sato Y 
Published: October 2024

Abstract

Aim
This study aims to assess the plaque morphology of non-target lesions, especially lipid-core-containing plaque (LCP), and compare it to target lesions using near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) in patients with femoropopliteal disease.

Methods
We conducted a single-center prospective observational study on 14 patients who underwent endovascular therapy for femoropopliteal disease between July 2022 and November 2023. NIRS-IVUS assessment was performed on the whole femoropopliteal arterial segment. Forty-one LCP lesions &gt; maximum lipid-core burden index in any 4-mm region (max LCBI4mm) 100 were detected by NIRS-IVUS. We evaluated patient and lesion characteristics. In addition, the LCP lesions were divided into two groups, the target lesion group (n=18) and the non-target lesion group (n=23), and compared.

Results
Patient characteristics were notable for advanced age (76.8±6.6 years), high incidence of male (78.7%), hypertension (100%), dyslipidemia (78.6%), diabetes (64.3%), statin use (71.4%). Lipid profiles were as follows: LDL-cholesterol 85.9±26.7 mg/dl, HDL-cholesterol 48.9±12.7 mg/dl, triglyceride 138.9±80.3 mg/dl, lipoprotein(a) 19.6±16.3 mg/dl. Ten participants had LCPs in the non-target lesion (71.4%). For IVUS findings, the target lesion group had significantly longer lesion length (34.6±11.9 mm vs. 22.6±8.7 mm, p=0.001), smaller minimum lumen area (7.0±2.8 mm2 vs. 14.8±5.4 mm2, p&lt;0.001), and larger plaque burden (78.0±5.0 % vs. 53.0±12.0 %, p&lt;0.001) than those in the non-target lesion group. No significant differences were observed in the prevalence of calcification (target lesion group vs. non-target lesion group: 83.3 % vs. 91.3 %, p=0.64) and the extent of calcification (p=0.76). For NIRS findings, the target lesion group contained a significantly smaller proportion of LCP in the lesion length (25.9±15.7 % vs. 50.6±29.2 %, p=0.002) than the non-target lesion group. On the other hand, there were no significant differences in the value of max LCBI4mm (284.4±153.4 vs. 289.5±113.1, p=0.90) and the length of LCP lesion (9.8±9.7 mm vs. 10.7±6.9 mm, p=0.74) and distribution of LCP (p=0.08) between both groups. In addition, the number of LCPs in the target femoropopliteal artery was positively correlated with max LCBI4mm in the target femoropopliteal artery (r=0.671, p=0.008)

Conclusion
NIRS-IVUS findings in this study demonstrated that the non-target lesions contained LCPs to the same degree as the target lesions.
Effect of glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors and their combination on carotid intima-media thickness
Authors: Ikonomidis I , Papageorgiou A , Pavlidis G , Katogiannis K , Thymis J , Pliouta L , Kountouri A , Korakas E , Kostelli G , Michalopoulou E , Prentza V , Katsanaki E , Vlachomitros D , Stamoulis K , Lambadiari V 
Published: October 2024

Abstract

Background/Introduction
Type 2 diabetes mellitus (T2DM) is an additional factor for exacerbation of atherosclerosis increasing the risk for ischemic attacks such as coronary artery disease and ischemic stroke. Evaluation of carotid artery atherosclerosis through ultrasound techniques is a useful tool for risk stratification in type 2 diabetic patients.

Purpose
We investigated the effects of insulin, glucagon like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on carotid intima-media thickness (cIMT) of T2DM patients.

Methods
A total of 320 T2DM patients were randomized to receive insulin (n = 80), liraglutide (n = 80), empagliflozin (n = 80) or their combination (GLP-1RA+SGLT-2i) (n = 80) as add-on to metformin. At baseline, at 6 and at 12 months of treatment, we measured the maximal thickness of six major points including right and left common carotid, carotid bifurcation and internal carotids. Finally, we calculated the average cIMT of all six segments (three on each side) to get mean cIMT.

Results
Compared to baseline, all patients had significantly reduced cIMT at 6 and at 12 months of treatment (p &lt; 0.001; Table). A significant interaction of follow-up time with the type of treatment was observed regarding cIMT levels (F = 7.203, p for interaction &lt; 0.001) in a model including age, sex, smoking, baseline body mass index, glucose levels, glycosylated hemoglobin, levels of blood lipids and their changes at 6 and 12 months of treatment as covariates. At 6 months, patients who were treated with GLP-1RA, SGLT-2i and those under the combination GLP-1RA+SGLT-2i showed a greater reduction of cIMT (-2.5%, -2.4% and -5.8%) compared to insulin (-0.8%; p = 0.008, p = 0.022, and p &lt; 0.001, respectively). Moreover, at 12 months patients under GLP-1RA, SGLT-2i and their combination achieved remarkable reduction of cIMT (-7.4%, -4.9% and -10%) than those under insulin (-1.7%, p &lt; 0.001 for all comparisons).

Conclusions
Twelve-month treatment with GLP-1RA, SGLT-2i and their combination resulted in reduction of cIMT in T2DM. The combined treatment was superior and additive to each regimen separately.Table
Preclinical assessment of transcatheter-delivered expandable endoluminal polymeric graft fabricated by electrospinning of microfiber
Authors: Miyashita K , Revaiah P , Sanders B , Tobe A , Basum G , Vries R , Onuma Y , Serruys P 
Published: October 2024

Abstract

Background
Matrix fabricated from electrospinning of micro fibre of polyester is porous and permeable to blood, facilitates cell infiltration and late resorption of the biodegradable material. This biomaterial opens an avenue of research in recreating a novel and favourable endoluminal lining in diseased vessel.
Previous preclinical work has shown that implants in aorta of rodents generate layers of endoluminal elastin. In humans, one of the most impervious arteries to atherosclerosis is the intra-thoracic artery; therefore, an attempt to induce similar structures with an implantable device was made.

Methods
For this study, novel tissue-engineered vascular grafts (T-TEVGs) were used in a preclinical rabbit iliac artery model. It was made of resorbable polyester biomaterial processed into fibrous tubular conduits. These T-TEVGs were implanted percutaneously. In total, twelve T-TEVGs in iliac arteries of nine rabbits were implanted. Follow-up were conducted on five rabbits with eight T-TEVGs at three months, two rabbits with two T-TEVGs at six months, and two rabbits with two T-TEVGs at twelve months. At follow-up, percutaneous optical coherence tomography (OCT) was performed, and OCT-derived luminal vessel wall dimensions and fractional flow reserve (OFR) derived from OCT were assessed.

Results
The overall pooled analysis at different timepoints on follow-up, documented an average MLA of 1.74±0.48mm2, average of proximal and distal reference area of 4.55±0.99 mm2, average area stenosis of 61±12%, and mean OFR value of 0.96±0.03 (OFR ranging from 0.89 to 0.99).
There was a moderate positive correlation between minimum lumen area and OFR (r=0.590, p&lt; 0.01). There was a strong negative correlation between percentage area stenosis and OFR (r= - 0.846, p&lt; 0.01). At no timepoint in follow-up and in every vessel analysed, OFR value was lower than 0.89, suggesting that none of these vessels exhibited flow-limiting narrowing.
Our study has a few limitations. 1) The preclinical model is a non-atherosclerotic rabbit; 2) There was no barotrauma prior to the implantation of the device; 3) Limited sample size, short and medium follow-up duration, and pooling of assessment at different timepoints.

Conclusion
The current study shows the durability and favourable hemodynamics of this bioresorbable fibrillated scaffold at short and medium term follow-up, supporting the potential utility of T-TEVEGs for peripheral human artery revascularisation. Long-term follow-ups are mandatory to confirm the durability of these results. Histopathology of this preclinical model should confirm the endoluminal elastin as previously documented in rodents (rats) and will be presented at the time of the congress.
Drug-eluting devices versus angioplasty in infrapopliteal artery disease:an updated systematic review and meta-analysis
Authors: Katsuyama E , Fukunaga C , Andrade N , Petri R , Cardoso C 
Published: October 2024

Abstract

Background
Clinically driven target lesion revascularization (CD-TLR) and restenosis are common complications in individuals with chronic limb-threatening ischemia (CLTI) and infrapopliteal artery disease undergoing percutaneous transluminal angioplasty (PTA). Drug-eluting balloons, stents, and resorbable scaffolds have emerged as an alternative therapy that may decrease the recurrence of these complications compared to PTA. However, their efficacy and safety are still controversial.

Purpose
This study aims to update and provide new insights about coated balloons, stents, and resorbable scaffolds as drug-eluting devices compared to PTA in patients with CLTI and infrapopliteal artery disease.

Methods
We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing drug-eluting devices, such as stents, coated balloons, and resorbable scaffolds, to PTA in patients with CLTI and infrapopliteal artery disease. The primary endpoint of interest was (1) CD-TLR. We only included trials defining this outcome as angiographically confirmed restenosis associated with wound changes or change in Rutherford classification at 12 months follow-up. This study also reported the following secondary outcomes: (2) binary restenosis and (3) amputation. We performed a subgroup analysis of the drug-eluting devices and between the drug-eluting pharmacological class, comparing the limus drug family subgroup and Pactlitaxel subgroup.

Results
We included 6 RCTs, encompassing 1263 patients, of whom 761 (60.2%) received a drug-eluting device. The mean age was 70.94 years. In the pooled analysis, the primary endpoint of CD-TLR was not statistically significant(OR 0.79; 95% CI 0.56-1.12; p=0.64; figure 1A). Although binary restenosis (OR: 0.62; 95% CI 0.36-1.05; p= 0.04; Fig.1B) was not statistically significant, our subgroup analysis of different drug-eluting pharmacological classes was significantly different(p&lt;0.01; Fig.1B). Furthermore, the -limus family subgroup presented with a significant lower (OR 0.39; 95% CI 0.25 - 0.61; p&lt;0.01; Fig. 1B) binary restenosis. There was no significant difference in the amputation endpoint (OR: 1.12; 95% CI 0.52 - 2.49; p= 0.74) and among the drug-eluting devices subgroup (p=0.63; Fig. 1A) for the CD-TLR endpoint.

Conclusion
In this updated meta-analysis of patients with CLTI and infrapopliteal artery, drug-eluting devices were not associated with CD-TLR compared to PTA. However, the -limus drug family is associated with a more significant reduction in the binary restenosis endpoint.
Intraplaque hemorrhage in carotid atherosclerotic plaques is associated with a local increase in inflammatory cytokines
Authors: Nardi V , Mahmoudi Hamidabad N , Di Venanzio L , Copley E A , Tiwari A , Rajai N , Rajotia A , Lutgens E , Lerman L O , Lerman A 
Published: October 2024

Abstract

Background
One of the main features of vulnerability in atherosclerotic carotid plaques is intraplaque hemorrhage (IPH), which is related to a higher incidence of cerebrovascular events in patients with carotid artery disease. Additionally, inflammation plays a pivotal role in the progression of atherosclerotic disease.

Purpose
We aimed to determine plasma and tissue levels of inflammatory cytokines in patients with carotid artery disease hypothesizing that plaques with IPH are characterized by the presence of a more inflamed environment.

Methods
We retrospectively enrolled 104 consecutive patients undergoing carotid endarterectomy (CEA) with symptomatic (ischemic stroke, TIA, amaurosis fugax) or asymptomatic ipsilateral carotid artery disease. Plasma and carotid plaque specimens were collected at CEA. The tissue samples were stained with H&E to identify IPH and classified as specimens with and without IPH.
Frozen homogenates of both plasma and tissue were analyzed using a customized 10-plex Luminex assay to determine the levels of inflammatory cytokines such as MCP-1/CCL2, IL-8/CXCL8, IFN-gamma, IL-10, IL-1beta/IL-1F2, IL-6, PDGF-AA, PDGF-AB/BB, TNF-alpha, and VEGF.

Results
IPH was identified in 53 patients (51.0 %). Cytokine levels in plasma and tissue from patients with and without IPH are reported in Table 1. In the univariate logistic regression MCP-1/CCL2, IL-8/CXCL8, IFN-gamma, IL-10, IL6, PDGF-AA, and PDGF-AB/BB were associated with IPH (Table 2). In the multivariate logistic regression, IL-6 was an independent predictor of IPH (HR 1.026 [95% CI 1.005-1.047]; p=0.014) after adjusting for cardiovascular risk factors such as age, BMI, sex, hypertension, diabetes mellitus, hyperlipidemia, ipsilateral carotid stenosis %.

Conclusions
Carotid plaques with IPH have an elevated inflammatory burden, potentially impacting adverse outcomes in this patient cohort. The local inflammatory cytokines in carotid plaques with IPH might serve as biomarkers and therapeutic targets in patients with carotid artery disease.
Apolipoprotein C3-rich low-density lipoprotein (AC3RL) exacerbates cerebral ischaemic stroke injury by increasing BBB leakage via LOX-1
Authors: Tsai P H , Tseng K F , Lin M C , Chang Y H , Cheng C W , Chen F Y , Shen M Y 
Published: October 2024

Abstract

Background
Ischaemic stroke causes the abrupt reduction or cessation of blood flow to the brain results in a cascade of events that can compromise blood-brain barrier (BBB) integrity. We revealed that an increase in apolipoprotein C3 (ApoC3)-rich low-density lipoprotein (AC3RL) is associated with endothelial cell apoptosis and inflammatory responses, indicating that AC3RL is one of the risk factors for cardiovascular events. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) triggers a cascade of events within endothelial cells that leads to endothelial dysfunction.

Purpose
We aimed to investigate whether AC3RL affects BBB permeability via the LOX-1, and thus increases brain damage.

Methods
We collected the whole blood from normal and patients with ischaemic events and separated them by centrifugation. AC3RL were collected using FPLC. We performed middle cerebral artery occlusion (MCAO) surgery to induce ischaemic stroke using B6 (C57BL/6) and LOX-1-/- mice injected with AC3RL. Triphenyl tetrazolium chloride (TTC) and Evans blue stains were accessed to confirm brain injury and BBB permeability.

Results
FPLC results showed that patients with ischaemic events presented higher levels of AC3RL compared to normal people. TTC stain showed the increased area of ischaemic penumbra damage in B6 mice with AC3RL injection, and LOX-1-/- mice with AC3RL injection were significantly protected. Evans blue dye leakage was observed in the brain tissues of B6 mice with AC3RL injection. LOX-1-/- mice with AC3RL injection revealed a decrease in BBB permeability. The modified neurological severity score (mNSS) method revealed a significant rise in B6 mice with AC3RL injection, which suggested a decline in motor and nervous function. LOX-1-/- mice with AC3RL injection significantly improved in motor and neurological functioning.

Conclusions
We demonstrate that AC3RL, through its effects on LOX-1, is associated with an increased risk of BBB damage after stroke. Therefore, pharmacological inhibition of AC3RL-LOX-1 interaction will be the main strategy to reduce severe brain damage.
Figure 1: (A) AC3RL percentage (%) in individuals. Normal: healthy people, Ischemic event: patients who have experienced an ischemic event. **p &lt; 0.001 vs. Normal group. (B, C) TTC stain of brain tissue after euthanasia to pinpoint the site of brain damage. The white portion of the mice brains indicated the site of the injury. (D, E) Evans blue dye leakage study in mice brains exhibited BBB permeability changes. (F) Assessment of mice's motor and neurological performance using the mNSS. Data are expressed as the mean ± SEM. **p &lt; 0.001, ****p &lt; 0.0001 vs. sham group, ##p &lt; 0.001 vs. B6 I.V. AC3RL group.Graphical abstractFigure 1.
Cardiac autonomic changes after stroke
Authors: Schreinlechner M , Theurl F , Massmann C , Dolejsi T , Hofer F , Tessadri C , Bauer A 
Published: October 2024

Abstract

Introduction
There is a highly complex and clinically important relationship between the cardiac and the nervous system, called the heart-brain axis [1]. Therefore, acute brain damage may lead to alterations in cardiac function due to changes in the autonomic nervous system[2,3]. Novel computerised biosignal analysis techniques and advanced biosignal assessment could provide a valuable tool to sensitively analyse cardiac autonomic function (CAF). CAF can be characterized by two complementary digital biomarkers, periodic repolariation dynamics (PRD) and deceleration capacity (DC). The aim of this study was to determine CAF by means of PRD and DC in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) and to analyze them according to their relationship with specific cardiac (high-sensitive Troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-pro BNP)) and stroke (location, type, severity) characteristics.

Methoden / Methods
Between February 22, 2021, and May 5, 2023, 282 patients after an AIS or TIA were enrolled in the study. During the inpatient stay, all relevant parameters were recorded and stored in a database. To assess CAF, a 30-minute biosignal measurement was performed with a high resolution (1kHz) electrocardiogram (ECG). Cardiac autonomic biomarkers, PRD and DC, were calculated semiautomatically afterwards from patients.

Results
Fifteen ECGs were excluded due to poor recording quality. Consequently, data from 261 AIS and 21 TIA patients were analyzed. A total of 105 patients (37.2 %) had pathological PRD (≥ 5.75 deg2) and/or DC (≤ 2.5 ms), 78 patients (27.7 %) had pathological PRD, and 57 patients (20.2 %) had pathological DC. The median PRD was 3.13 deg2 and the median DC was 5.30 ms (see Figure). There were no significant differences in the distribution of PRD and DC between male and female patients (PRD p = 0.38, DC p = 0.30), and between AIS and TIA patients (PRD p = 0.13, DC p = 0.66). Patients with middle cerebral artery (MCA) infarction had significantly higher median PRD values (3.56 deg2 [IQR 1.51 - 6.59 ] vs. 2.81 deg2 [IQR 1.15 - 5.99], p = 0.047) and lower median DC values (4.66 ms [IQR 2.65 – 7.76] vs. 6.11 ms [IQR 3.15 – 10.61], p = 0.011) than patients with stroke located in another cerebral regions (see Figure). Patients with pathological PRD or DC had significantly higher hsTnT (13.50 ng/l [IQR 9.7 – 24.1] vs. 11.05 ng/l [ IQR 7.13 – 16.23], p &lt; 0.001) and NT-pro BNP (269.00 ng/l [IQR 117.50 – 687.00] vs. 125.50 ng/l [IQR 57.00 – 288.25], p &lt; 0.001) values.

Conclusions
The study showed that a considerable proportion, more than one third of all patients, had evidence of cardiac autonomic dysfunction after acute cerebral ischaemia. Of particular interest, PRD was higher and DC was lower in patients with MCA ischaemia, reflecting a potentially higher cardiac risk profile. Cardiac autonomic dysfunction was also associated with increased hsTnT and NT-proBNP levels.