Superparamagnetic iron oxide nanoparticles have diverse diagnostic and potential therapeutic applications in the central nervous system (CNS). They are useful as magnetic resonance imaging (MRI) ...contrast agents to evaluate: areas of blood–brain barrier (BBB) dysfunction related to tumors and other neuroinflammatory pathologies, the cerebrovasculature using perfusion-weighted MRI sequences, and in vivo cellular tracking in CNS disease or injury. Novel, targeted, nanoparticle synthesis strategies will allow for a rapidly expanding range of applications in patients with brain tumors, cerebral ischemia or stroke, carotid atherosclerosis, multiple sclerosis, traumatic brain injury, and epilepsy. These strategies may ultimately improve disease detection, therapeutic monitoring, and treatment efficacy especially in the context of antiangiogenic chemotherapy and antiinflammatory medications. The purpose of this review is to outline the current status of superparamagnetic iron oxide nanoparticles in the context of biomedical nanotechnology as they apply to diagnostic MRI and potential therapeutic applications in neurooncology and other CNS inflammatory conditions.
Purpose:
We aimed to examine the effectiveness of different therapeutic options for and to identify the possible risk factors of recurrent internal carotid artery (ICA) in-stent restenosis (ISR).
...Methods:
Forty-six ICA ISRs, which were reintervened at least once, were retrospectively analyzed regarding clinical and imaging characteristics, as well as invasive treatment type (percutaneous transluminal angioplasty PTA with a plain balloon, PTA with a drug-eluting balloon DEB, re-stenting) used.
Results:
The median follow-up was 29.5 months (IQR, 8.5-52.8 months) in patients who underwent reintervention for ICA ISR. Stent occlusion occurred in 3 patients (6.5%). One ISR recurrence was noted in 10 patients (21.7%); reintervention was carried out in 7 cases (7/10 70%; PTA, N = 5; PTA with a DEB, N = 1; re-stenting, N = 1), while 3 patients (3/10; 30%) received best medical treatment. Two ISR recurrences were observed in 3 patients (6.5%); all of them underwent reintervention (PTA, N = 1; PTA with a DEB, N = 2). Three ISR recurrences were seen in 1 patient (2.2%), who was treated with PTA. No recurrence was observed in those patients, who had DEB treatment. Multiple logistic regression analysis revealed statin therapy to be a protective factor against recurrent ISR (OR, 0.17; 95% CI, 0.03-0.84; P = .029).
Conclusion:
Our study suggests that PTA with a DEB is the most effective for the treatment of recurrent ISR, and confirms the importance of statin use in patients who have had a carotid reintervention.
Our aim was to identify the incidence of and predictors for common carotid artery (CCA) stent fractures (SFs) and to examine the effect of SFs on the development of in-stent restenosis (ISR).
Seventy ...patients (37 women; median age, 60.9 years) who were stented for significant (≥60%) proximal CCA stenosis from 2006 to 2016 and revisited us to determine SF using fluoroscopy in 2018 were evaluated. Seventy stents were deployed; among them 87.1% were balloon-expandable and 12.9% were self-expandable. SFs were classified as type I (fracture of one strut), type II (fracture of multiple struts without stent deformity), type III (fracture of multiple struts with stent deformity), type IV (complete fracture of the stent without a gap), and type V (complete fracture of the stent with a gap). Duplex ultrasound examination was used for monitoring stent patency. Mann-Whitney U and Fisher's exact tests, Kaplan-Meier and logistic regression analyses, and a log-rank test and a gamma correlation analysis were applied as statistical methods.
The patients were followed for 75.5 months (range, 47-109 months). Significant (≥70%) ISR was observed in eight patients (11.4%). Reintervention was performed in four cases (5.7%). Twenty-seven SFs (38.6%; type I, 8; type II, 10; type III, 4; type IV, 2; and type V, 3) were found. Calcification was shown to be a significant predictor for SF (odds ratio, 13.2; 95% confidence interval, 3.9-45.1; P < .001). There was no significant difference between the fractured and the nonfractured group regarding the number of patients with ISR and reintervention (P = .701 and P = .636, respectively). Neither did the primary patency rates differ significantly (P = .372) in patients with and without SF.
Fractures frequently occur in a wide variety of stent devices deployed in the proximal CCA, but SFs seem to have no effect on ISR and reintervention.
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Ferumoxytol, an ultrasmall superparamagnetic iron oxide particle, has been suggested as a potential alternative MRI contrast agent in patients with renal failure. We compared ferumoxytol to ...gadoteridol enhancement on T1- and T2-weighted MRI in CNS disorders to explore its diagnostic utility.
Data were collected from three protocols in 70 adults who underwent alternate-day gadoteridol- and ferumoxytol-enhanced MRI using identical parameters. Two neuroradiologists measured lesion-enhancing size and intensity on contrast-enhanced T1-weighted images in consensus. T2-weighted images were evaluated for the presence of contrast-enhanced hypointensity. Mixed model repeated measures analysis of variance determined differences between T1-weighted enhancement size and intensity for individual protocols and group.
After exclusions, 49 MRI studies in 29 men and 20 women (mean age, 51 years) were assessed. T1-weighted estimated enhancing sizes were different between agents (p = 0.0456) as a group; however, no differences were observed with untreated gliomas (n = 17) in two protocols (p = 1.0 and p = 0.99, respectively). Differences in T1-weighted enhancement intensity between agents were significant for the group overall (p = 0.0006); however, three-way interactions were not significant (p = 0.1233). T2-weighted images were assessed for contrast-enhanced hypointensity, observed in 26 of 49 (53%) ferumoxytol and zero of 49 (0%) gadoteridol scans.
Ferumoxytol may be a useful MRI contrast agent in patients who are unable to receive gadolinium-based contrast agents. Greater experience with a wider variety of disorders is necessary to understand differences in enhancement with ferumoxytol compared with gadolinium-based contrast agents, given their different mechanisms of action.
Abstract
Background and aim
There is only a limited number of major publications on the outcome of interventions for isolated popliteal artery stenosis. The purpose of this study was to report our ...results on mid-term patency and predictors of restenosis.
Patients and methods
This single-center retrospective study included 61 symptomatic patients (males,
N
= 33; median age, 65.1 years IQR, 60.7–71.9 years; Rutherford grade 4–6,
N
= 14) with at least two patent crural arteries, whose atherosclerotic stenoses/occlusions were treated with percutaneous transluminal angioplasty (PTA) or stenting (using self-expanding bare-metal Astron Pulsar stents) between 2011 and 2018.
Results
Twenty-six patients had PTA, while 35 underwent stenting. The median follow-up was 29 months (IQR, 10–47 months). The primary patency rates were not significantly different (
P
= 0.629) between PTA and stenting groups. Restenosis developed in nine patients (34.6%) in the PTA group, and in 12 (34.3%) in the stenting group. Restenotic lesions required re-intervention in nine cases (100%) in the PTA group, and in eight (66.7%) in the stenting group. Restenosis developed significantly less frequently (
P
= 0.010) in patients with a popliteal/P1 stent; the primary patency rates were also significantly better (
P
= 0.018) in patients with a popliteal/P1 stent when compared to popliteal/P2 plus multi-segment stents. Cox regression analysis identified lesion location as a predictor of in-stent restenosis (HR, 2.5; 95% CI, 1.2–5.5;
P
= 0.019).
Conclusion
Stenting was not superior when compared to PTA (if selective stenting was not considered as loss of patency). Follow-up should be more thorough in patients undergoing popliteal/P2 or multi-segment stenting.
Human induced pluripotent stem cell-derived endothelial cells can be candidates for engineering therapeutic vascular grafts.
Here, we studied the role of three-dimensional culture on their ...characteristics and function both
and
.
We found that differentiated hPSC-EC can re-populate decellularized biomatrices; they remain viable, undergo maturation and arterial/venous specification. Human PSC-EC develop antifibrotic, vasoactive and anti-inflammatory properties during recellularization.
, a robust increase in perfusion was detected at the engraftment sites after subcutaneous implantation of an hPSC-EC-laden hydrogel in rats. Histology confirmed survival and formation of capillary-like structures, suggesting the incorporation of hPSC-EC into host microvasculature. In a canine model, hiPSC-EC-seeded onto decellularised vascular segments were functional as aortic grafts. Similarly, we showed the retention and maturation of hiPSC-EC and dynamic remodelling of the vessel wall with good maintenance of vascular patency.
A combination of hPSC-EC and biomatrices may be a promising approach to repair ischemic tissues.
Mannose-binding lectin (MBL) is thought to influence the pathophysiology of cardiovascular disease by decreasing the risk of advanced atherosclerosis and by contributing to enhanced ischemia ...reperfusion injury. Thus, we investigated the role of MBL in restenosis after eversion endarterectomy in patients with severe carotid atherosclerosis.
In a prospective study, 123 patients who underwent carotid endarterectomy were followed-up by carotid duplex scan (CDS) sonography for 14 months. In a retrospective study, we examined 17 patients and 29 patients, respectively, who had or had not at least 50% restenosis 29 months after carotid eversion endarterectomy. MBL genotypes were analyzed by a polymerase chain reaction-based method, and MBL serum concentrations were measured.
In the prospective study in the patients homozygous for the normal MBL genotype, CDS values were significantly higher after 14 months of follow-up compared with the values measured 6 weeks after surgery (P<0.001). In contrast, only a slight increase was registered in patients carrying MBL variant alleles. The differences were much more pronounced in female than in male patients. Similar differences were observed when patients with high and low MBL serum concentrations were compared. In the retrospective study, a significant increase in the frequency of MBL variant genotypes was observed in patients not experiencing restenosis compared with the patients with restenosis (P=0.007).
These results indicate that reoccurrence of stenosis after carotid endarterectomy is partially genetically determined and imply that MBL contributes significantly to the pathophysiology of this condition.
To evaluate factors associated with pseudoaneurysm (PSA) development.
Between January 2016 and May 2020, 30,196 patients had invasive vascular radiological or cardiac endovascular procedures that ...required arterial puncture. All patients with PSA were identified. A matched (age, gender, and type of the procedure) control group of 134 patients was created to reveal predictors of PSA formation.
Single PSAs were found in 134 patients. Fifty-three PSAs developed after radiological procedures (53/6555 0.8%), 31 after coronary artery procedures (31/18038 0.2%), 25 after non-coronary artery cardiac procedures (25/5603 0.4%), and 25 due to procedures in which the arterial puncture was unintended. Thirty-four PSAs (25.4%) were localized to the upper extremity arteries (vascular closure device VCD, N = 0), while 100 (74.6%) arose from the lower extremity arteries (VCD, N = 37). The PSA prevalence was 0.05% (10/20478) in the radial artery, 0.1% (2/1818) in the ulnar artery, 1.2% (22/1897) in the brachial artery, and 0.4% (99/22202) in the femoral artery. Treatments for upper and lower limb PSAs were as follows: bandage replacement (32.4% and 14%, respectively), ultrasound-guided compression (11.8% and 1%, respectively), ultrasound-guided thrombin injection (38.2% and 78%, respectively), and open surgery (17.6% and 12%, respectively). Reintervention was necessary in 19 patients (14.2%). The prevalence of PSA for the punctured artery with and without VCD use was 37/3555 (1%) and 97/27204 (0.4%), respectively (OR, 2.94; 95% CI, 1.95-4.34; P<0.001). The effect of red blood cell (RBC) count (P<0.001), hematocrit value (P<0.001), hemoglobin value (P<0.001), international normalized ratio (INR; P<0.001), RBC count-INR interaction (P = 0.003), and RBC count-VCD use interaction (P = 0.036) on PSA formation was significant.
Patients in whom the puncture site is closed with a VCD require increased observation. Preprocedural laboratory findings are useful for the identification of patients at high risk of PSA formation.
OBJECTIVE:To describe and correlate neurotoxicity indicators in long-term primary CNS lymphoma (PCNSL) survivors who were treated with high-dose methotrexate–based regimens with or without ...whole-brain radiotherapy (WBRT).
METHODS:Eighty PCNSL survivors from 4 treatment groups (1 with WBRT and 3 without WBRT) who were a minimum of 2 years after diagnosis and in complete remission underwent prospective neuropsychological, quality-of-life (QOL), and brain MRI evaluation. Clinical characteristics were compared among treatments by using the χ test and analysis of variance. The association among neuroimaging, neuropsychological, and QOL outcomes was assessed by using the Pearson correlation coefficient.
RESULTS:The median interval from diagnosis to evaluation was 5.5 years (minimum, 2 years; maximum, 26 years). Survivors treated with WBRT had lower mean scores in attention/executive function (p = 0.0011), motor skills (p = 0.0023), and neuropsychological composite score (p = 0.0051) compared with those treated without WBRT. Verbal memory was better in survivors with longer intervals from diagnosis to evaluation (p = 0.0045). On brain imaging, mean areas of total T2 abnormalities were different among treatments (p = 0.0006). Total T2 abnormalities after WBRT were more than twice the mean of any non-WBRT group and were associated with poorer neuropsychological and QOL outcomes.
CONCLUSIONS:Our results suggest that in patients treated for PCNSL achieving complete remission and surviving at least 2 years, the addition of WBRT to methotrexate-based chemotherapy increases the risk of treatment-related neurotoxicity. Verbal memory may improve over time.
CLASSIFICATION OF EVIDENCE:This study provides Class III evidence that in patients treated for PCNSL achieving complete remission and surviving at least 2 years, the addition of WBRT to methotrexate-based chemotherapy increases the risk of treatment-related neurotoxicity.
To provide information on the outcomes of upper and lower limb surgical embolectomies and the factors influencing amputation and mortality.
A retrospective, single-center analysis of 347 patients ...(female, N = 207; male, N = 140; median age, 76 years interquartile range {IQR}, 63.2-82.6 years) with acute upper or lower limb ischemia due to thromboembolism who underwent surgery between 2005 and 2019 was carried out. Patient demographics, comorbidities, medical history, the severity of acute limb ischemia (ALI), preoperative medication regimen, embolus/thrombus localization, procedural data, in-hospital complications/adverse events and their related interventions, and 30-day mortality were reviewed in electronic medical records. Statistical analysis was performed using the Mann-Whitney U test and Fisher's exact test; in addition, univariate and multivariate logistic regression was conducted.
The embolus/thrombus was localized to the upper limb in 134 patients (38.6%) and the lower limb in 213 patients (61.4%). The median length of hospital stay was 3.8 days (IQR, 2.1-6.6 days). The in-hospital major amputation rates for the upper limb, lower limb, and total patient population were 2.2%, 14.1%, and 9.5%, respectively, and the in-hospital plus 30-day mortality rates were 4.5%, 9.4%, and 7.5%, respectively. In patients with lower limb embolectomy, the predictor of in-hospital major amputation was the time between the onset of symptoms and embolectomy (OR, 1.78), while the predictor of in-hospital plus 30-day mortality was previous stroke (OR, 7.16). In the overall patient cohort, there were two predictors of in-hospital major amputation: 1) the time between the onset of symptoms and embolectomy (OR, 1.92) and 2) compartment syndrome (OR, 3.51).
Amputation and mortality rates after surgical embolectomies in patients with ALI are high. Patients with prolonged admission time, compartment syndrome, and history of stroke are at increased risk of limb loss or death. To avoid amputation and death, patients with ALI should undergo surgical intervention as soon as possible and receive close monitoring in the peri- and postprocedural periods.
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