Abstract
BACKGROUND:
Intrinsic thrombosis and stenosis are complications associated with the use of neck-remodeling devices in the treatment of intracranial aneurysms.
OBJECTIVE:
To examine the ...technical and anatomic factors that predict short- and long-term stent patency.
METHODS:
We undertook a retrospective review of 161 patients who underwent coil embolization of 168 ruptured and unruptured aneurysms assisted by the use of a neck-remodeling device. One hundred twenty-seven patients had catheter-based angiographic follow-up to evaluate 133 stent-coil constructs (mean, 15.4 months; median, 12.7 months). The technique of microcatheter jailing was used in a majority of patients; nonstandard stent configurations were also used.
RESULTS:
Clinical follow-up for all patients who had catheter-based angiograms demonstrated that among 133 stent constructs, a total of 9 (6.8%) had an in-stent event: 6 acute or subacute thrombosis (4.5%) and 3 delayed stenosis or occlusion (2.3%). Seven of these constructs were associated with a symptomatic event (5.3%). A significantly higher rate of in-stent events was seen with the use of constructs to treat anterior communicating artery aneurysms. When all patients are considered, including those who did not receive catheter-based follow-up imaging, 2 of 168 procedures (1.2%) resulted in the death of a patient, and procedural morbidity was 14.9%.
CONCLUSION:
From these results and those in the published literature, in-stent complication rates are low in carefully selected patients. The use of dual antiplatelet therapy, sensitivity assays, and glycoprotein IIb/IIIa inhibitors may decrease the rate of acute and chronic in-stent complications.
National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-31 suggested the efficacy of adjuvant trastuzumab, even in HER2-negative breast cancer. This finding prompted us to develop a ...predictive model for degree of benefit from trastuzumab using archived tumor blocks from B-31.
Case subjects with tumor blocks were randomly divided into discovery (n = 588) and confirmation cohorts (n = 991). A predictive model was built from the discovery cohort through gene expression profiling of 462 genes with nCounter assay. A predefined cut point for the predictive model was tested in the confirmation cohort. Gene-by-treatment interaction was tested with Cox models, and correlations between variables were assessed with Spearman correlation. Principal component analysis was performed on the final set of selected genes. All statistical tests were two-sided.
Eight predictive genes associated with HER2 (ERBB2, c17orf37, GRB7) or ER (ESR1, NAT1, GATA3, CA12, IGF1R) were selected for model building. Three-dimensional subset treatment effect pattern plot using two principal components of these genes was used to identify a subset with no benefit from trastuzumab, characterized by intermediate-level ERBB2 and high-level ESR1 mRNA expression. In the confirmation set, the predefined cut points for this model classified patients into three subsets with differential benefit from trastuzumab with hazard ratios of 1.58 (95% confidence interval CI = 0.67 to 3.69; P = .29; n = 100), 0.60 (95% CI = 0.41 to 0.89; P = .01; n = 449), and 0.28 (95% CI = 0.20 to 0.41; P < .001; n = 442; P(interaction) between the model and trastuzumab < .001).
We developed a gene expression-based predictive model for degree of benefit from trastuzumab and demonstrated that HER2-negative tumors belong to the moderate benefit group, thus providing justification for testing trastuzumab in HER2-negative patients (NSABP B-47).
There are few existing data on the status of coronary artery disease (CAD) in patients with atherosclerosis of the cerebral artery detected by brain imaging studies. We aimed to analyze the ...predictors of asymptomatic angiographically significant CAD detected by simultaneous cerebral and coronary angiography.
This retrospective cohort study screened data obtained between August 2009 and April 2019; 11,047 patients underwent cerebral angiography for atherosclerotic change (>50% stenosis or aneurysm) seen in brain magnetic resonance angiography (MRA) or computed tomography angiography (CTA) at a single center by endovascular neurosurgeon's decision. Of these, 700 patients including 622 patients who underwent simultaneous coronary and cerebral angiography and 78 patients who underwent coronary angiography within a month were enrolled. We investigated the characteristics and predictors of angiographically significant CAD (>50% stenosis). Furthermore, we also analyzed the major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause death, myocardial infarction, and stroke for 5 years.
The frequency of significant CAD was 59% (413/700), the mean age was 68.9 ± 10.3 years, and 60.6% were male. During mean follow-up of 50 months, the MACCE rate of our whole cohort was significantly higher in the CAD group (21.5%) than in the non-CAD group (14.6%; hazard ratio 1.65, 95% CI 1.17-2.33, p value = 0.005). Considering that the embolic stroke is less associated with atherosclerotic change, our predictive model of significant CAD was made without embolic stroke (n = 599). In our multivariate model 2 including univariate <0.1, the independent predictors of significant CAD were male (OR 1.62, 95% CI 1.11-2.35, p = 0.012), diabetes mellitus (OR 1.81, 95% CI 1.22-2.68, p = 0.003), previous stroke (OR 1.63, 95% CI 1.02-2.60, p = 0.039), low ankle-brachial index (ABI; <0.9; OR 3.25, 95% CI 1.21-8.73, p = 0.019), left ventricular ejection fraction (EF) <50% on echocardiography (OR 2.82, 95% CI 1.25-6.35, p = 0.012), troponin I or T positive (OR 2.76, 95% CI 1.69-4.53, p < 0.001), and complex features on cerebral angiography (OR 2.73, 95% CI 1.78-4.19, p < 0.001).
Accurate coronary evaluation by coronary angiography might be considered when patients with atherosclerotic cerebral artery detected on brain MRA or CTA planned cerebral angiography were male or have diabetes mellitus, previous stroke, low ABI (<0.9), left ventricular EF <50% on echocardiography, troponin I or T positivity, and complex features on cerebral angiography.
Tissue regeneration is an essential requirement for wound healing and recovery of organs' function. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling ...mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O
and 5% CO
). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor-β, and vascular endothelial growth factor responsible for skin regeneration were much higher (10-30 folds) in the ERCM than in normal conditioned medium (NCM). In was found that CM-DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H
O
cytotoxicity. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated, remaining minimal crusts, by topical application of ERCM solution (4 × 10
exosome particles/100 μL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. In addition, enhanced angiogenesis in ERCM-treated wounds was confirmed by increased von Willebrand factor (vWF)-positive endothelial cells. The results indicate that ERCM from AMSCs with high concentrations of GFs and NFs improves wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production, in addition to the regulation of angiogenesis and scar tissue formation.
The cytokine inducible SH2‐domain protein (CISH) is a well‐known STAT5 target gene, but its role in the immune system remains uncertain. In this study, we found that CISH is predominantly induced ...during dendritic cell (DC) development from mouse bone marrow (BM) cells and plays a crucial role in type 1 DC development and DC‐mediated CTL activation. CISH knockdown reduced the expression of MHC class I, co‐stimulatory molecules and pro‐inflammatory cytokines in BMDCs. Meanwhile, the DC yield was markedly enhanced by CISH knockdown via cell‐cycle activation and reduction of cell apoptosis. Down‐regulation of cell proliferation at the later stage of DC development was found to be associated with CISH‐mediated negative feedback regulation of STAT5 activation. In T‐cell immunity, OT‐1 T‐cell proliferation was significantly reduced by CISH knockdown in DCs, whereas OT‐2 T‐cell proliferation was not affected by CISH knockdown. CTLs generated by DC vaccination were also markedly reduced by CISH knockdown, followed by significant impairment of DC‐based tumor immunotherapy. Taken together, our data suggest that CISH expression at the later stage of DC development triggers the shutdown of DC progenitor cell proliferation and facilitates DC differentiation into a potent stimulator of CTLs.
Therapeutic decision for adjuvant systemic therapy for breast cancer involves assessment of baseline risk and estimated benefit from systemic therapy. Molecular profiling studies have clearly ...demonstrated heterogeneity of chemotherapy response across different molecular subtypes of breast cancer. Meta-analyses of publicly available data from gene expression profiling studies have demonstrated that breast cancer can be divided into 4 basic categories based on expression levels of estrogen receptor (ER), HER2, and proliferation-associated genes; ER-, HER2+, ER+/HER2-/low proliferation, and ER+/HER2-/high proliferation. Notably ER- or HER2+ tumors are associated with high levels expression of proliferation genes, although there is a wide spectrum of expression levels of proliferation genes among ER+/HER2- tumors. Estrogen receptor-positive/HER2-/low-proliferation tumors are associated with a favorable prognosis. Synthetic lethal screening approach has demonstrated that most of the chemotherapeutic agents do not have specific molecular targets. Therefore, it could be hypothesized that chemosensitivity would be largely dictated by proliferation activity of tumor cells. Therefore, tumors with ER-, HER2+, or ER+/HER2-/high proliferation gene expression profile can be categorized as chemosensitive tumors, whereas ER+/HER-/low proliferation tumors categorized as chemoresistant. Therefore, clinical utility of gene expression profiling is mainly in aiding the chemotherapy decision for ER+ patients. Although evidence from prospective randomized clinical trials are lacking, because of the excellent baseline prognosis of patients with ER+/HER2-/low proliferation tumors when treated with endocrine therapy and because of scientific evidence of chemoresistance of these tumors, a comfort zone has been reached among oncologists to allow clinical use of gene expression tests to identify patients who do not require chemotherapy among node-negative ER+ patients. However, these tools are still probabilistic at best in their performances, and one cannot exactly predict which patient will have recurrence after assigned therapies until the time of recurrence. Therefore, strategies have to be established to identify patients who will fail standard chemoendocrine therapies among high-risk patients (ER+/HER2-/high proliferation, HER2+, or ER-) before recurrence events. Neoadjvant therapy can provide such venue because regardless of regimens used the prognosis of those achieving complete pathological response is excellent. Postneoadjuvant setting can be then used for patients with gross residual disease to test novel therapeutic agents.
Purpose
Spontaneous vertebrobasilar dissecting aneurysm (VBD) is a very challenging disease with an unpredictable clinical course and controversies on treatment strategy. The present study reports ...radiological and clinical outcomes of stent-alone treatment (SAT) for VBD.
Methods
Twenty-four VBDs treated with SAT are included in the present study. Clinical and angiographic data were reviewed retrospectively.
Results
A total of 24 lesions in 22 patients with a mean follow-up period of 16.21 months were included. Of the 24 individual lesions, 23 were intracranial vertebral artery lesions and 1 lesion was located in the basilar artery. There were six cases of ruptured dissections with the other cases having various symptoms. The immediate post-SAT angiographic outcomes included 5 lesions with good remodeling over 90% recovery and 19 poorly remodeled lesions. The latest angiographic outcomes included 17 cases of good remodeling (remodeling rate over 90%), 6 cases of poor remodeling (remodeling rate below 70%), and 1 case with morphological aggravation. The overlapping stent technique was used in seven cases and it was significantly associated with good angiographic results. None of the rupture cases underwent re-rupture post SAT. There was one case of a symptomatic complication of a femoral arteriovenous fistula.
Conclusions
The SAT could be a feasible alternative for the treatment of VBD. The overlapping technique was significantly associated with good angiographic outcome. We expect that technological development of the intracranial stent will allow better procedural outcomes of SAT.
Since ginsenosides exert an anti-thrombotic activity, blood flow-improving effects of DK-MGAR101, an extract of mountain ginseng adventitious roots (MGAR) containing various ginsenosides, were ...investigated in comparison with an extract of Korean Red Ginseng (ERG).
In Sprague-Dawley rats orally administered with DK-MGAR101 or ERG, oxidative carotid arterial thrombosis was induced with FeCl3 (35%), and their blood flow and occlusion time were measured. To elucidate underlying mechanisms, the cytoprotective activities on rat aortic endothelial cells (RAOECs) exposed to hydrogen peroxide (H2O2) were confirmed. In addition, the inhibitory activities of DK-MGAR101 and ERG on agonist-induced platelet aggregation, thromboxane B2 production, and ATP granule release from stimulated platelets as well as blood coagulation were analyzed.
DK-MGAR101 containing high concentrations of Rb1, Rg1, Rg3, Rg5, and Rk1 ginsenosides (55.07 mg/g) was more effective than ERG (ginsenosides 8.45 mg/g) in protecting RAOECs against H2O2 cytotoxicity. DK-MGAR101 was superior to ERG not only in suppressing platelet aggregation, thromboxane B2 production, and granule release, but also in delaying blood coagulation, FeCl3-induced arterial occlusion, and thrombus formation.
The results indicate that DK-MGAR101 prevents blood vessel occlusion by suppressing platelet aggregation, thrombosis, and blood coagulation, in addition to endothelial cell injury.
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