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Glial TIM-3 Modulates Immune Responses in the Brain Tumor Microenvironment

T-cell immunoglobulin and mucin domain–containing molecule 3 (TIM-3), a potential immunotherapeutic target for cancer, has been shown to display diverse characteristics in a context-dependent manner. Thus, it would be useful to delineate the precise functional features of TIM-3 in a given situation. Here, we report that glial TIM-3 shows distinctive properties in the brain tumor microenvironment. TIM-3 was expressed on both growing tumor cells and their surrounding cells including glia and T cells in an orthotopic mouse glioma model. The expression pattern of TIM-3 was distinct from those of other immune checkpoint molecules in tumor-exposed and tumor-infiltrating glia. Comparison of cells from tumor-bearing and contralateral hemispheres of a glioma model showed that TIM-3 expression was lower in tumor-infiltrating CD11b+CD45mid glial cells but higher in tumor-infiltrating CD8+ T cells. In TIM-3 mutant mice with intracellular signaling defects and Cre-inducible TIM-3 mice, TIM-3 affected the expression of several immune-associated molecules including iNOS and PD-L1 in primary glia-exposed conditioned media (CM) from brain tumors. Further, TIM-3 was cross-regulated by TLR2, but not by TLR4, in brain tumor CM- or Pam3CSK4-exposed glia. In addition, following exposure to tumor CM, IFNγ production was lower in T cells cocultured with TIM-3–defective glia than with normal glia. Collectively, these findings suggest that glial TIM-3 actively and distinctively responds to brain tumor, and plays specific intracellular and intercellular immunoregulatory roles that might be different from TIM-3 on T cells in the brain tumor microenvironment.Significance:TIM-3 is typically thought of as a T-cell checkpoint receptor. This study demonstrates a role for TIM-3 in mediating myeloid cell responses in glioblastoma.




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Targeting the E3 Ubiquitin Ligase PJA1 Enhances Tumor-Suppressing TGF{beta} Signaling

RING-finger E3 ligases are instrumental in the regulation of inflammatory cascades, apoptosis, and cancer. However, their roles are relatively unknown in TGFβ/SMAD signaling. SMAD3 and its adaptors, such as β2SP, are important mediators of TGFβ signaling and regulate gene expression to suppress stem cell–like phenotypes in diverse cancers, including hepatocellular carcinoma (HCC). Here, PJA1, an E3 ligase, promoted ubiquitination and degradation of phosphorylated SMAD3 and impaired a SMAD3/β2SP-dependent tumor-suppressing pathway in multiple HCC cell lines. In mice deficient for SMAD3 (Smad3+/−), PJA1 overexpression promoted the transformation of liver stem cells. Analysis of genes regulated by PJA1 knockdown and TGFβ1 signaling revealed 1,584 co-upregulated genes and 1,280 co-downregulated genes, including many implicated in cancer. The E3 ligase inhibitor RTA405 enhanced SMAD3-regulated gene expression and reduced growth of HCC cells in culture and xenografts of HCC tumors, suggesting that inhibition of PJA1 may be beneficial in treating HCC or preventing HCC development in at-risk patients.Significance: These findings provide a novel mechanism regulating the tumor suppressor function of TGFβ in liver carcinogenesis.




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Systemic Immune Response and Cancer Risk: Filling the Missing Piece of Immuno-Oncology

While immuno-oncology has made significant advances in activating local tumor immune responses, leading to improved outcomes, the role of systemic immunity in cancer incidence remains poorly understood. Le Cornet and colleagues prospectively studied circulating immune cells quantified by DNA methylation markers in relation to incidence of breast, colorectal, lung, and prostate cancer among initially healthy individuals. A positive association with cancer risk was observed for higher FOXP3+ T-cell–mediated immune tolerance and lower CD8+ T-cell–mediated cytotoxicity. Further studies of systemic immunity in cancer development are crucial to identify novel prediction markers and interventional targets for cancer immunoprevention.See related article by Le Cornet et al., p. 1885




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Immunotherapeutic Response in Tumors Is Affected by Microenvironmental ROS

Carcinoma-associated fibroblasts (CAF) are a potential therapeutic target for both direct and indirect regulation of cancer progression and therapy response. In this issue of Cancer Research, Ford and colleagues investigate the influence of CAF on the immune environment of tumors, specifically focusing on the regulation of CD8+ T cells, required for immune therapy response. Their work suggests a role for stromally expressed NADPH oxidase 4 (NOX4) as a modulator of reactive oxygen species that in turn can reduce the number of CD8+ T cells locally. Inhibition of NOX4 increased CD8+ T cells and restored responsiveness to immune therapy, suggesting an indirect stromally targeted avenue for therapy resensitization.See related article by Ford et al., p. 1846




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Cancer Research




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Increased Notching of the Corpus Callosum in Fetal Alcohol Spectrum Disorder: A Callosal Misunderstanding? [PEDIATRICS]

BACKGROUND AND PURPOSE:

In the medicolegal literature, notching of the corpus callosum has been reported to be associated with fetal alcohol spectrum disorders. Our purpose was to analyze the prevalence of notching of the corpus callosum in a fetal alcohol spectrum disorders group and a healthy population to determine whether notching occurs with increased frequency in the fetal alcohol spectrum disorders population.

MATERIALS AND METHODS:

We performed a multicenter search for cases of fetal alcohol spectrum disorders and included all patients who had a sagittal T1-weighted brain MR imaging. Patients with concomitant intracranial pathology were excluded. The corpus callosum was examined for notches using previously published methods. A 2 test was used to compare the fetal alcohol spectrum disorders and healthy groups.

RESULTS:

Thirty-three of 59 patients with fetal alcohol spectrum disorders (0–44 years of age) identified across all centers had corpus callosum notching. Of these, 8 had an anterior corpus callosum notch (prevalence, 13.6%), 23 had a posterior corpus callosum notch (prevalence, 39%), and 2 patients demonstrated undulated morphology (prevalence, 3.4%). In the healthy population, the anterior notch prevalence was 139/875 (15.8%), posterior notch prevalence was 378/875 (43.2%), and undulating prevalence was 37/875 (4.2%). There was no significant difference among the anterior (P = .635), posterior (P = .526), and undulating (P = .755) notch prevalence in the fetal alcohol spectrum disorders and healthy groups.

CONCLUSIONS:

There was no significant difference in notching of the corpus callosum between patients with fetal alcohol spectrum disorders and the healthy population. Although reported to be a marker of fetal alcohol spectrum disorders, notching of the corpus callosum should not be viewed as a specific finding associated with fetal alcohol spectrum disorders.




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Advanced ADC Histogram, Perfusion, and Permeability Metrics Show an Association with Survival and Pseudoprogression in Newly Diagnosed Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium [FUNCTIONAL]

BACKGROUND AND PURPOSE:

Diffuse intrinsic pontine glioma is a lethal childhood brain cancer with dismal prognosis and MR imaging is the primary methodology used for diagnosis and monitoring. Our aim was to determine whether advanced diffusion, perfusion, and permeability MR imaging metrics predict survival and pseudoprogression in children with newly diagnosed diffuse intrinsic pontine glioma.

MATERIALS AND METHODS:

A clinical trial using the poly (adenosine diphosphate ribose) polymerase (PARP) inhibitor veliparib concurrently with radiation therapy, followed by maintenance therapy with veliparib + temozolomide, in children with diffuse intrinsic pontine glioma was conducted by the Pediatric Brain Tumor Consortium. Standard MR imaging, DWI, dynamic contrast-enhanced perfusion, and DSC perfusion were performed at baseline and approximately every 2 months throughout treatment. ADC histogram metrics of T2-weighted FLAIR and enhancing tumor volume, dynamic contrast-enhanced permeability metrics for enhancing tumors, and tumor relative CBV from DSC perfusion MR imaging were calculated. Baseline values, post-radiation therapy changes, and longitudinal trends for all metrics were evaluated for associations with survival and pseudoprogression.

RESULTS:

Fifty children were evaluable for survival analyses. Higher baseline relative CBV was associated with shorter progression-free survival (P = .02, Q = 0.089) and overall survival (P = .006, Q = 0.055). Associations of higher baseline mean transfer constant from the blood plasma into the extravascular extracellular space with shorter progression-free survival (P = .03, Q = 0.105) and overall survival (P = .03, Q = 0.102) trended toward significance. An increase in relative CBV with time was associated with shorter progression-free survival (P < .001, Q < 0.001) and overall survival (P = .004, Q = 0.043). Associations of longitudinal mean extravascular extracellular volume fraction with progression-free survival (P = .03, Q = 0.104) and overall survival (P = .03, Q = 0.105) and maximum transfer constant from the blood plasma into the extravascular extracellular space with progression-free survival (P = .03, Q = 0.102) trended toward significance. Greater increases with time were associated with worse outcomes. True radiologic progression showed greater post-radiation therapy decreases in mode_ADC_FLAIR compared with pseudoprogression (means, –268.15 versus –26.11, P = .01.)

CONCLUSIONS:

ADC histogram, perfusion, and permeability MR imaging metrics in diffuse intrinsic pontine glioma are useful in predicting survival and pseudoprogression.




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Comparison of Enhancement of the Vestibular Perilymph between Variable and Constant Flip Angle-Delayed 3D-FLAIR Sequences in Meniere Disease [HEAD & NECK]

BACKGROUND AND PURPOSE:

Endolymphatic hydrops in patients with Menière disease relies on delayed postcontrast 3D-FLAIR sequences. The purpose of this study was to compare the degree of perilymphatic enhancement and the detection rate of endolymphatic hydrops using constant and variable flip angles sequences.

MATERIALS AND METHODS:

This was a retrospective study performed in 16 patients with Menière disease who underwent 3T MR imaging 4 hours after gadolinium injection using two 3D-FLAIR sequences with a constant flip angle at 140° for the first and a heavily-T2 variable flip angle for the second. The signal intensity ratio was measured using the ROI method. We graded endolymphatic hydrops and evaluated the cochlear blood-labyrinth barrier impairment.

RESULTS:

Both for symptomatic and asymptomatic ears, the median signal intensity ratio was significantly higher with the constant flip angle than with the heavily-T2 variable flip angle (7.16 versus 1.54 and 7.00 versus 1.45, P < .001). Cochlear blood-labyrinth barrier impairment was observed in 4/18 symptomatic ears with the heavily-T2 variable flip angle versus 8/19 with constant flip angle sequences. With heavily-T2 variable flip angle sequences, endolymphatic hydrops was observed in 7–10/19 symptomatic ears versus 12/19 ears with constant flip angle sequences. We found a significant association between the clinical symptomatology and the presence of endolymphatic hydrops with constant flip angle but not with heavily-T2 variable flip angle sequences. Interreader agreement was always perfect with constant flip angle sequences while it was fair-to-moderate with heavily-T2 variable flip angle sequences.

CONCLUSIONS:

3D-FLAIR constant flip angle sequences provide a higher signal intensity ratio and are superior to heavily-T2 variable flip angle sequences in reliably evaluating the cochlear blood-labyrinth barrier impairment and the endolymphatic space.




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Assessment of Apparent Internal Carotid Tandem Occlusion on High-Resolution Vessel Wall Imaging: Comparison with Digital Subtraction Angiography [EXTRACRANIAL VASCULAR]

BACKGROUND AND PURPOSE:

Not all tandem occlusions diagnosed on traditional vascular imaging modalities, such as MRA, represent actual complete ICA occlusion. This study aimed to explore the utility of high-resolution vessel wall imaging in identifying true ICA tandem occlusions and screening patients for their suitability for endovascular recanalization.

MATERIALS AND METHODS:

Patients with no signal in the ICA on MRA were retrospectively reviewed. Two neuroradiologists independently reviewed their high-resolution vessel wall images to assess whether there were true tandem occlusions and categorized all cases into intracranial ICA occlusion, extracranial ICA occlusion, tandem occlusion, or near-occlusion. DSA classified patient images into the same 4 categories, which were used as the comparison with high-resolution vessel wall imaging. The suitability for recanalization of occluded vessels was evaluated on high-resolution vessel wall imaging compared with DSA.

RESULTS:

Forty-five patients with no ICA signal on MRA who had available high-resolution vessel wall imaging and DSA images were included. Among the 34 patients (34/45, 75.6%) with tandem occlusions on DSA, 18 cases also showed tandem occlusions on high-resolution vessel wall imaging. The remaining 16 patients, intracranial ICA, extracranial ICA occlusions and near-occlusions were found in 2, 6, and 8 patients, respectively, on the basis of high-resolution vessel wall imaging. A total of 20 cases (20/45, 44.4%) were considered suitable for recanalization on the basis of both DSA and high-resolution vessel wall imaging. Among the 25 patients deemed unsuitable for recanalization by DSA, 11 were deemed suitable for recanalization by high-resolution vessel wall imaging.

CONCLUSIONS:

High-resolution vessel wall imaging could allow identification of true ICA tandem occlusion in patients with an absence of signal on MRA. Findings on high-resolution vessel wall imaging can be used to screen more suitable candidates for recanalization therapy.




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Intermixed Dimethyl-Sulfoxide-Based Nonadhesive Liquid Embolic Agents Delivered Serially via the Same Microcatheter for Cerebral AVM Treatment [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Conventional nonadhesive liquid embolic agents currently are the criterion standard for endovascular embolization of cerebral AVMs. However, inadequate distal penetration into the nidus and unstable proximal plug formation are the major limitations of this approach and of the currently available embolic materials. The aim of this study was to evaluate the hypothetic efficacy of combining liquid embolic agents with different properties and viscosities for use in endovascular embolization of cerebral AVMs.

MATERIALS AND METHODS:

From March 2018 to March 2019, sixteen patients with cerebral AVMs (12 women, 4 men; age range, 33–61 years) underwent endovascular embolization with combined liquid embolic agents delivered serially via a single microcatheter. The procedure consists of initial embolization with PHIL 30%, followed by Menox 18 through the same microcatheter. According to the Spetzler-Martin scale, 11 (68.75%) AVMs were grades I–II, 4 (25%) were grade III, and 1 (6.25%) was grade IV. Angiographic, technical, and clinical outcomes were analyzed independently.

RESULTS:

Combined PHIL and Menox embolization through the same microcatheter via 21 pedicles was performed in these 16 patients. Once the length of the reflux reached approximately 2 cm, PHIL 30% was switched to Menox 18. Antegrade flow and distal penetration of the serially applied liquid embolic agents were observed in all 16 cases. The ability to completely control the flow of the materials and avoid any dangerous proximal reflux was noted in all performed embolizations. The estimated average size reduction of the treated AVMs was 85%, ranging from 50% to 100%. Complete embolization was achieved in 10/16 or 62.5% of the cases. There was no procedure-related complication during or after the embolization. No mortality or postprocedural clinical worsening was seen. Clinical success and complete obliteration were confirmed with at least 1 follow-up angiography in 10/16 patients.

CONCLUSIONS:

Serial delivery of nonadhesive liquid embolic agents via the same microcatheter was safe and effective in our study and may be a potential technique for routine AVM treatment. However, further investigations are required to validate the safety and the efficacy of the method.




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Glasgow Coma Scale on Presentation Predicts Outcome in Endovascular Treatment for Acute Posterior Large-Vessel Occlusion [INTERVENTIONAL]

SUMMARY:

Use of mechanical thrombectomy for stroke has increased since the publication of trials describing outcome improvement when used in the anterior circulation. These results, however, cannot be directly translated to the posterior circulation. While a high NIHSS score has demonstrated an association with poor outcomes in posterior stroke, the NIHSS is weighted toward hemispheric disease, and complex scores potentially delay definitive imaging diagnosis. We performed a retrospective analysis to ascertain whether any rapidly obtainable demographic or clinical and imaging data have a correlation with patient outcome postthrombectomy. Seventy-three cases were audited between September 2010 and October 2017. Presenting with a Glasgow Coma Scale score of >13 meant that the odds of reaching the primary end point of functional independence (defined as a 90-day modified Rankin Scale score of 0–2) were 5.70 times greater; similarly, presenting with a posterior circulation ASPECTS of >9 resulted in the odds of reaching the primary end point being 4.03 times greater. Older age correlated to a lower odds of independence (0.97, p = .04).




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White Matter Disease and Outcomes of Mechanical Thrombectomy for Acute Ischemic Stroke [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

The increased severity of white matter disease is associated with worse outcomes and an increased rate of intracerebral hemorrhage in patients with ischemic stroke undergoing thrombolytic treatment. However, whether white matter disease is associated with outcomes in patients undergoing endovascular treatment remains unclear.

MATERIALS AND METHODS:

In this prespecified exploratory analysis of our prospective multi-institutional study that enrolled consecutive adult patients with anterior circulation ischemic stroke undergoing endovascular treatment from November 2017 to September 2018, we compared the following outcomes between patients with none-to-minimal (van Swieten score, 0–2) and moderate-to-severe (van Swieten score, 3–4) white matter disease using logistic regression: 90-day mRS 3–6, death, intracerebral hemorrhage, successful recanalization, and early neurologic recovery.

RESULTS:

Of the 485 patients enrolled in the Blood Pressure after Endovascular Stroke Therapy (BEST) study, 389 had white matter disease graded (50% women; median age, 68 years; range, 58–79 years). A van Swieten score of 3–4 (n = 74/389, 19%) was associated with a higher rate of 90-day mRS of 3–6 (45% versus 18%; adjusted OR, 2.73; 95% CI, 1.34–5.93; P = .008). Although the death rate was higher in patients with van Swieten scores of 3–4 (26% versus 15%), the adjusted likelihood was not significantly different (adjusted OR, 1.14; 95% CI, 0.56–2.26; P = .710). Ordered regression revealed a shift toward worse mRS scores with increasing van Swieten scores (adjusted common OR, 3.04; 95% CI, 1.93–4.84; P < .001). No associations between white matter disease severity and intracerebral hemorrhage, successful recanalization, and early neurologic recovery were observed.

CONCLUSIONS:

Moderate-to-severe white matter disease is associated with worse outcomes in patients undergoing endovascular treatment without a significant increase in hemorrhagic complications. Studies comparing patients with and without endovascular treatment are necessary to determine whether the benefit of endovascular treatment is attenuated with greater white matter disease.




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Contrast-Induced Acute Kidney Injury in Radiologic Management of Acute Ischemic Stroke in the Emergency Setting [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

The use of invasive cerebral angiography with CTA for active treatment of patients with suspected ischemic strokes has been increasing recently. This study aimed to identify the incidence of postcontrast acute kidney injury using baseline renal function when CTA and cerebral angiography were performed sequentially.

MATERIALS AND METHODS:

This retrospective observational study evaluated adults (18 years of age or older) with ischemic stroke who underwent CTA and cerebral angiography sequentially between 2010 and 2018. The incidence of postcontrast acute kidney injury was determined using the baseline estimated glomerular filtration rate. The value of the baseline estimated glomerular filtration rate at which the occurrence of postcontrast acute kidney injury increased was also determined.

RESULTS:

Postcontrast acute kidney injury occurred in 57/601 (9.5%) patients. Those with a baseline estimated glomerular filtration rate of <30 mL/min/1.73 m2 showed a higher incidence of acute kidney injury. Age, chronic kidney disease, medication (nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β blockers, statins, and insulin) use following contrast media exposure, and serum albumin affected the incidence of postcontrast acute kidney injury. The incidence of postcontrast acute kidney injury increased when the baseline estimated glomerular filtration rate was <43 mL/min/1.73 m2.

CONCLUSIONS:

Patients with low baseline renal function had the highest incidence of postcontrast acute kidney injury after CTA and cerebral angiography, but no fatal adverse effects were documented. Thus, patients suspected of having a stroke should be actively managed with respect to neurovascular function.




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MRI Vessel Wall Imaging after Intra-Arterial Treatment for Acute Ischemic Stroke [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Vessel wall imaging is increasingly performed in the diagnostic work-up of patients with ischemic stroke. The aim of this study was to compare vessel wall enhancement after intra-arterial thrombosuction with that in patients not treated with thrombosuction.

MATERIALS AND METHODS:

From 2009 to 2017, forty-nine patients with an ischemic stroke underwent 7T MR imaging within 3 months after symptom onset as part of a prospective intracranial vessel wall imaging study. Fourteen of these patients underwent intra-arterial treatment using thrombosuction (intra-arterial treatment group). In the intra-arterial treatment group, vessel walls were evaluated for major vessel wall changes. All patients underwent pre- and postcontrast vessel wall imaging to assess enhancing foci of the vessel wall using coregistered subtraction images. A Wilcoxon signed rank test was performed to test for differences.

RESULTS:

In the intra-arterial treatment group, 11 of 14 patients (79%) showed vessel wall enhancement compared with 17 of 35 patients without intra-arterial treatment (49%). In the intra-arterial treatment group, more enhancing foci were detected on the ipsilateral side (n = 18.5) compared with the contralateral side (n = 3, P = .005). Enhancement was more often concentric on the ipsilateral side (n = 8) compared with contralateral side (n = 0, P = .01). No differences were found in the group without intra-arterial treatment between the number and configuration of ipsilateral and contralateral enhancing foci.

CONCLUSIONS:

Patients with intra-arterial treatment by means of thrombosuction showed more (concentric) enhancing foci of the vessel wall ipsilateral compared with contralateral to the treated artery than the patients without intra-arterial treatment, suggesting reactive changes of the vessel wall. This finding should be taken into account when assessing vessel wall MR images in patients with stroke.




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Reliability of CT Angiography in Cerebral Vasospasm: A Systematic Review of the Literature and an Inter- and Intraobserver Study [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Computed tomography angiography offers a non-invasive alternative to DSA for the assessment of cerebral vasospasm following subarachnoid hemorrhage but there is limited evidence regarding its reliability. Our aim was to perform a systematic review (Part I) and to assess (Part II) the inter- and intraobserver reliability of CTA in the diagnosis of cerebral vasospasm.

MATERIALS AND METHODS:

In Part I, articles reporting the reliability of CTA up to May 2018 were systematically searched and evaluated. In Part II, 11 raters independently graded 17 arterial segments in each of 50 patients with SAH for the presence of vasospasm using a 4-category scale. Raters were additionally asked to judge the presence of any moderate/severe vasospasm (≥ 50% narrowing) and whether findings would justify augmentation of medical treatment or conventional angiography ± balloon angioplasty. Four raters took part in the intraobserver reliability study.

RESULTS:

In Part I, the systematic review revealed few studies with heterogeneous vasospasm definitions. In Part II, we found interrater reliability to be moderate at best ( ≤ 0.6), even when results were stratified according to specialty and experience. Intrarater reliability was substantial ( > 0.6) in 3/4 readers. In the per arterial segment analysis, substantial agreement was reached only for the middle cerebral arteries, and only when senior raters’ judgments were dichotomized (presence or absence of ≥50% narrowing). Agreement on the medical or angiographic management of vasospasm based on CTA alone was less than substantial ( ≤ 0.6).

CONCLUSIONS:

The diagnosis of vasospasm using CTA alone was not sufficiently repeatable among observers to support its general use to guide decisions in the clinical management of patients with SAH.




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CT Angiography in Evaluating Large-Vessel Occlusion in Acute Anterior Circulation Ischemic Stroke: Factors Associated with Diagnostic Error in Clinical Practice [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

It is currently not completely clear how well radiologists perform in evaluating large-vessel occlusion on CTA in acute ischemic stroke. The purpose of this study was to investigate potential factors associated with diagnostic error.

MATERIALS AND METHODS:

Five hundred twenty consecutive patients with a clinical diagnosis of acute ischemic stroke (49.4% men; mean age, 72 years) who underwent CTA to evaluate large-vessel occlusion of the proximal anterior circulation were included. CTA scans were retrospectively reviewed by a consensus panel of 2 neuroradiologists. Logistic regression analysis was performed to investigate the association between several variables and missed large-vessel occlusion at the initial CTA interpretation.

RESULTS:

The prevalence of large-vessel occlusion was 16% (84/520 patients); 20% (17/84) of large-vessel occlusions were missed at the initial CTA evaluation. In multivariate analysis, non-neuroradiologists were more likely to miss large-vessel occlusion compared with neuroradiologists (OR = 5.62; 95% CI, 1.06–29.85; P = .04), and occlusions of the M2 segment were more likely to be missed compared with occlusions of the distal internal carotid artery and/or M1 segment (OR = 5.69; 95% CI, 1.44–22.57; P = .01). There were no calcified emboli in initially correctly identified large-vessel occlusions. However, calcified emboli were present in 4 of 17 (24%) initially missed or misinterpreted large-vessel occlusions.

CONCLUSIONS:

Several factors may have an association with missing a large-vessel occlusion on CTA, including the CTA interpreter (non-neuroradiologists versus neuroradiologists), large-vessel occlusion location (M2 segment versus the distal internal carotid artery and/or M1 segment), and large-vessel occlusion caused by calcified emboli. Awareness of these factors may improve the accuracy in interpreting CTA and eventually improve stroke outcome.




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Discrimination between Glioblastoma and Solitary Brain Metastasis: Comparison of Inflow-Based Vascular-Space-Occupancy and Dynamic Susceptibility Contrast MR Imaging [FUNCTIONAL]

BACKGROUND AND PURPOSE:

Accurate differentiation between glioblastoma and solitary brain metastasis is of vital importance clinically. This study aimed to investigate the potential value of the inflow-based vascular-space-occupancy MR imaging technique, which has no need for an exogenous contrast agent, in differentiating glioblastoma and solitary brain metastasis and to compare it with DSC MR imaging.

MATERIALS AND METHODS:

Twenty patients with glioblastoma and 22 patients with solitary brain metastasis underwent inflow-based vascular-space-occupancy and DSC MR imaging with a 3T clinical scanner. Two neuroradiologists independently measured the maximum inflow-based vascular-space-occupancy–derived arteriolar CBV and DSC-derived CBV values in intratumoral regions and peritumoral T2-hyperintense regions, which were normalized to the contralateral white matter (relative arteriolar CBV and relative CBV, inflow-based vascular-space-occupancy relative arteriolar CBV, and DSC-relative CBV). The intraclass correlation coefficient, Student t test, or Mann-Whitney U test and receiver operating characteristic analysis were performed.

RESULTS:

All parameters of both regions had good or excellent interobserver reliability (0.74~0.89). In peritumoral T2-hyperintese regions, DSC-relative CBV (P < .001), inflow-based vascular-space-occupancy arteriolar CBV (P = .001), and relative arteriolar CBV (P = .005) were significantly higher in glioblastoma than in solitary brain metastasis, with areas under the curve of 0.94, 0.83, and 0.72 for discrimination, respectively. In the intratumoral region, both inflow-based vascular-space-occupancy arteriolar CBV and relative arteriolar CBV were significantly higher in glioblastoma than in solitary brain metastasis (both P < .001), with areas under the curve of 0.91 and 0.90, respectively. Intratumoral DSC-relative CBV showed no significant difference (P = .616) between the 2 groups.

CONCLUSIONS:

Inflow-based vascular-space-occupancy has the potential to discriminate glioblastoma from solitary brain metastasis, especially in the intratumoral region.




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Brain Metastases: Insights from Statistical Modeling of Size Distribution [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Brain metastases are a common finding on brain MRI. However, the factors that dictate their size and distribution are incompletely understood. Our aim was to discover a statistical model that can account for the size distribution of parenchymal metastases in the brain as measured on contrast-enhanced MR imaging.

MATERIALS AND METHODS:

Tumor volumes were calculated on the basis of measured tumor diameters from contrast-enhanced T1-weighted spoiled gradient-echo images in 68 patients with untreated parenchymal metastatic disease. Tumor volumes were then placed in rank-order distributions and compared with 11 different statistical curve types. The resultant R2 values to assess goodness of fit were calculated. The top 2 distributions were then compared using the likelihood ratio test, with resultant R values demonstrating the relative likelihood of these distributions accounting for the observed data.

RESULTS:

Thirty-nine of 68 cases best fit a power distribution (mean R2 = 0.938 ± 0.050), 20 cases best fit an exponential distribution (mean R2 = 0.957 ± 0.050), and the remaining cases were scattered among the remaining distributions. Likelihood ratio analysis revealed that 66 of 68 cases had a positive mean R value (1.596 ± 1.316), skewing toward a power law distribution.

CONCLUSIONS:

The size distributions of untreated brain metastases favor a power law distribution. This finding suggests that metastases do not exist in isolation, but rather as part of a complex system. Furthermore, these results suggest that there may be a relatively small number of underlying variables that substantially influence the behavior of these systems. The identification of these variables could have a profound effect on our understanding of these lesions and our ability to treat them.




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MR Thermometry in Cerebrovascular Disease: Physiologic Basis, Hemodynamic Dependence, and a New Frontier in Stroke Imaging [ADULT BRAIN]

SUMMARY:

The remarkable temperature sensitivity of the brain is widely recognized and has been studied for its role in the potentiation of ischemic and other neurologic injuries. Pyrexia frequently complicates large-vessel acute ischemic stroke and develops commonly in critically ill neurologic patients; the profound sensitivity of the brain even to minor intraischemic temperature changes, together with the discovery of brain-to-systemic as well as intracerebral temperature gradients, has thus compelled the exploration of cerebral thermoregulation and uncovered its immutable dependence on cerebral blood flow. A lack of pragmatic and noninvasive tools for spatially and temporally resolved brain thermometry has historically restricted empiric study of cerebral temperature homeostasis; however, MR thermometry (MRT) leveraging temperature-sensitive nuclear magnetic resonance phenomena is well-suited to bridging this long-standing gap. This review aims to introduce the reader to the following: 1) fundamental aspects of cerebral thermoregulation, 2) the physical basis of noninvasive MRT, and 3) the physiologic interdependence of cerebral temperature, perfusion, metabolism, and viability.




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Bán Shophouse chân đế Sky Oasis, trung tâm quảng trường nhìn ra Vịnh Đảo & Chợ Đêm. LH 0911938633

Cần bán căn shop đẹp nhất phía Đông Hà Nội tại Chân tòa chung cư Sky Oasis Ecopark. DT: Tổng 163m2 (2 tầng). Tầng 1: 82,4m2 - tầng 2: 81,1 m2. Hai tầng KD (tầng 1 cao 5m, tầng 2 cao 5.9m). Hình thức sở hữu: Sổ lâu dài, linh hoạt tách 2 sổ chuyển nhượng được. Đặc điểm: Gần bể bơi ...




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Sở hữu ngay Shophouse Metro Star mặt tiền Song Hành Xa Lộ Hà Nội giá chỉ 70 triệu/m2 Lh: 0933836751

Chỉ cần thanh toán 15% sở hữu ngay Shophouse Metro Star.- Chiết khấu lên đến 10%.- Cam kết cho thuê 111,305 triệu/tháng trong 3 năm.- Cam kết mua lại sau 24 tháng với lợi nhuận 22%.- Shophouse Metro Star vị trí vàng cửa ngõ khu Đông.- Nằm ngay mặt tiền Song Hành, Xa Lộ Hà Nội, li...




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Shophouse Green River quận 8, chung cư nằm trên mặt tiền Phạm Thế Hiển, phục vụ hơn 4000 cư dân

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Cần bán nhanh shophouse block B chung cư Citi Home, Phường Cát Lái, Quận 2, TP HCM

Cần bán nhanh shophouse block B chung cư Citi Home, Phường Cát Lái, Quận 2, TP HCM. Mã căn: B0 - 05, tầng trệt + lửng, block B thuộc dự án chung cư Citi Home, Phường Cát Lái, Quận 2, Tp HCM. Diện tích: Tổng 86.5m2. Được thiết kế vừa kinh doanh, vừa ở với diện tích tầng trệt 54,9m2, tầng lửng 31,6m2. Chung cư block B Citihome và các Block citihome bên cạnh với 17 tầng đã phủ đầy...




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Chính chủ cần bán Shophouse BG05, đang cho thuê giá 12tr/tháng. Thanh toán 50%, 1,1 tỷ thương lượng

Hiện đang thuê làm Nail và Tóc hợp đồng 3 năm tăng giá 10%. Ưu tiên khách mua giữ lại hợp đồng thuê vì mới gia hạn thêm 3 năm nữa. Chị thuê dễ thương, và sạch sẽ gọn gàng. Anh chị nào mua liên hệ chính chủ 0917424365 A Nhất. Các bạn môi giới chào khách dùm nhé, phí cao. Cảm ơn an...




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Duy nhất 1 căn Shophouse 90m2 GĐ1 của CĐT mặt tiền đường Xa Lộ Hà Nội Q9, đối diện ga Metro số 10

- Chủ đầu tư mở bán giai đoạn 1 duy nhất còn 1 căn diện tích 90m2 Shophouse Metro Star góc 2 mặt tiền tiện kinh doanh hoặc cho thuê sau này. - Shophouse Metro Star nằm đối diện trạm metro số 10 tuyến số 1 có cầu bộ hành kết nối trực tiếp vào tầng 2 của trung tâm thương mại của dự án. - Hiện tại tuyến Metro số 1 đã hoàn thiện hơn 70% tiến độ, dự kiến sẽ đi vào vận hành vào cuối ...




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Shophouse Metro Star, hot nhất khu Đông, cầu bộ hành nối liền tầng 2 của dự án vào nhà ga số 10

Lấy cảm hứng từ Myeongdong - khu phố mua sắm, giải trí nổi tiếng bậc nhất Seoul Một Myeongdong Hàn Quốc sẽ được tái hiện sống động ngay tại khu Đông Sài Gòn hứa hẹn tạo nên không gian sầm uất của phố thị rực rỡ.Tập trung hàng trăm thương hiệu thời trang nổi tiếng, không gian ẩm t...




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Cần bán Shophouse CC An Thịnh, An Phú An Khánh, Quận 2, TDT 201,9m2, hướng ĐN, sổ đỏ, giá 20 tỷ

- Cần bán Shophouse chung cư An Thịnh, An Phú An Khánh, Quận 2. Tổng diện tích 201,9m2, đường 20m (mặt tiền đường Thái Thuận giao nhau với đường Nguyễn Quý Đức) hướng Tây Bắc, sổ hồng, giá 20 tỷ. - Vị trí đẹp nhất ở quận 2, thích hợp mở quán cafe, mini shop... Gần Metro, trường h...




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Cần bán shophouse Park Hill 2 mặt tiền, đã có sổ đỏ

Mình cần bán gấp shophouse căn góc 2 mặt tiền Times City, Park Hill 8, quận Hai Bà Trưng - Hà Nội, đã có sổ đỏ. Diện tích: 100m2 x 2 tầng. Phía trước là đài phun nước; sân chơi nước kết hợp trình diễn ánh sáng; quảng trường ánh sáng, khu vui chơi trẻ em Vinperland, sân vui ...




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Bán shophouse Homyland 3 ngay trung tâm Quận 2, vô cùng phù hợp để kinh doanh, DT 90m2 giá 7.5 tỷ

Em Nhi chuyên bán căn hộ Homyland 3, shophouse, căn hộ officetel. Gọi ngay 0944 589 718 (zalo). Vị trí Homyland đắc địa ngay khu dân cư sầm uất, rất dễ kinh doanh mở quán café. Hiện tại giỏ hàng công ty em có. Cho thuê căn 02 - 40 triệu, 03 - 30 triệu, 08 - 30 triệu, 09 - 35 triệ...




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Bán shophouse Midtown - The Signature M7 Phú Mỹ Hưng - Shop 44 - 45.9 tỷ 0946.699.009

Bán ShopHouse căn 44 - Toà nhà hình trứng - The Signature M7, vị trí đẹp độc nhất dự án Midtown Phú Mỹ Hưng. Phú Mỹ Hưng Midtown nằm trên thế đất địa linh, vượng khí sinh tài lộc mà không phải dự án nào trong Phú Mỹ Hưng cũng sở hữu: + Cách một cây cầu là đến khu Thương mại...




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Shophouse TM mặt đường Võ Chí Công sở hữu lâu dài, mặt trước toà chung cư Udic Westlake. 0982943269

Shophouse mặt đường Võ Chí Công, mặt trước chung cư cao cấp Udic Westlake, xây thông 3 tầng, nhận bàn giao luôn, đặc biệt cấp sổ đỏ sở hữu lâu dài. Duy nhất 14 lô. Liên hệ PKD: 0982943269. -----------------------------* Tổng quan dự án: Tên dự án: Shophouse khối đế chung cư cao c...




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Bán shophouse Udic Westlake mặt đường Võ Chí Công, 3 tầng, 300m2, nhận nhà ngay, sổ đỏ lâu dài

Bán shophouse Udic Westlake mặt đường Võ Chí Công, đối diện trung tâm thương mại Lotte đang triển khai. Shophouse 3 tầng, mặt sàn trung bình 100m2, tổng diện tích từ 280m2 đến 350m2. Hướng Đông Nam, hướng mặt đường Võ Chí Công. Mặt tiền từ 7,2m đến 10m. Hiện đã hoàn thành và bàn ...




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Chính chủ cần tiền bán lỗ shophouse Hope Garden (Phúc Yên 3) giá rẻ 3.2 tỷ ( giá mua HĐ gần 3,4 tỷ)

Tôi cần tiền nên bán gấp shophouse Hope Garden (Phúc Yên 3) mặt tiền đường Phan Huy Ích - Diện tích: 80m2. - Bàn giao phần thô có thể xây dựng thêm 1 tầng lửng- Mặt tiền đường tiện mở văn phòng, công ty, coffee shop, siêu thị...- An ninh bảo vệ 24/24, bảo trì bảo dưỡng cần luôn ...




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Ra mắt shophouse 2 mặt tiền hot nhất Ecopark, Văn Giang, Hưng Yên

Mở bán Shophouse 2 Mặt tiền dự án Sky Oasis thuộc khu đô thị Ecopark. Nhanh tay sở hữu ngay shop chân đế vĩnh viễn. Diện tích 40 - 150m2. Nằm trên tuyến phố đi bộ 2.5km thiết kế phong cách Hàn, Nhật theo chủ đề. Phố shoping, giải trí, Check - in... Lưu lượng 10 tòa chung cư với h...




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Cần bán shophouse The Sun Avenue - Giá tốt nhất 5.8 tỷ - 0903989800

Thông tin mô tả. Quản lý 100% căn hộ tại dự án The Sun Avenue, Mai Chí Thọ, quận 2. Chúng tôi cam kết sẽ đem lại dịch vụ cho thuê và mua bán với giá cả tốt nhất thị trường, liên hệ phòng kinh doanh căn hộ The Sun Avenue gọi 0903 989 800.Nhận ký gửi mua bán cho thuê giao dịch nhan...




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Shophouse Phạm Thế Hiển ở liền - giữ tiền cho anh chị mùa Covid. LH ngay em: 0901 636 577

Bán shophouse mặt tiền quận 8 thanh toán 3,4 tỷ. Còn lại trả góp. - Hình thức: 1 trệt 1 lầu (được xây thêm 1 lửng). - Sổ hồng vĩnh viễn.Diện tích 151m2 đối diện công viên, gần trường học và dân cư và lưu lượng khách vài ngàn người mỗi ngày.Liên hệ: Mỹ Linh: Trưởng phòng kinh doan...




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Cho thuê Vinhomes Central Park - 1,2,3,4 PN, penthouse, với giá tốt, LH: 0909060957

Call Mr. Thanh: 0909 060 957 (Hotline tư vấn trực tuyến).Thông tin chi tiết giá thuê Vinhomes Central Park:- 1 phòng ngủ (48m2 - 53m2): 13tr - 16tr.- 2 phòng ngủ (68m2 - 89m2): 16tr - 19tr - 22tr.- 3 phòng ngủ (98m2 - 110m2 - 128m2): Chỉ từ 23tr.- 4 phòng ngủ (150m2 - 180 m2): Ch...




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Quản lý 100% giỏ hàng căn hộ Sunrise Riverside 10tr/th căn 2PN-12TR/th,căn 3PN -16TR/th.0982598959

Chuyên cho thuê căn hộ Sunrise Riverside - Novaland. - Căn hộ 55m2 - 2PN + 1WC. + Nội thất cơ bản: 9tr - 11 triệu/tháng. + Đầy đủ nội thất: 11.5tr - 13 triệu/tháng.- Căn hộ 70m2, 72m2 - 2PN + 2WC. + Nội thất cơ bản: 10tr - 12 triệu/tháng. + Đầy đủ nội thất: 12tr - 16 triệu/tháng....




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Senturia Nam Sài Gòn

Senturia Nam Sài Gòn là dự án có quy mô 19,8ha nằm trên đường Nguyễn Văn Linh, Bình Hưng, Bình Chánh.




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Royal Landmark & Shophouse Quảng Bình

Dự án Royal Landmark & Shophouse Quảng Bình là Tổ hợp nhà phố thương mại shophouse kết hợp kinh doanh khách sạn nghỉ dưỡng, dịch vụ thương mại nằm ngay bên bờ sông Nhật Lệ, TP. Đồng Hới (Quảng Bình).




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CÔNG TY TNHH CITY HOUSE VIỆT NAM

City House Việt Nam là đơn vị chuyên tư vấn, phân phối dự án căn hộ cao cấp Quận 1, Quận 2, Quận 3, Quận 7, Quận 9. Là đối tác của các chủ đầu tư uy tín như: Sunshine Group, Novaland, Kepple Land, Capitaland, Refico,...

Chuyên: Tư vấn, môi giới, đấu giá bất động sản, đấu giá quyền sử dụng đất

Với tiêu chí “Uy tín – Chuyên nghiệp – Sự khác biệt”, mục tiêu của City House Việt Nam là mang đến cho khách hàng sản phẩm và dịch vụ tốt nhất, những thông tin chuẩn xác nhất về thị trường BĐS.

Khu vực môi giới tốt nhất hiện nay:

+ Mua bán đất Quận 2
+ Bán đất nền dự án Quận 2
+ Bán nhà mặt phố Quận 2
+ Bán nhà riêng Quận Bình Thạnh
+ Bán nhà biệt thự, liền kề Quận Bình Thạnh
+ Bán nhà biệt thự, liền kề Quận 2
+ Bán căn hộ chung cư quận 7
+ Bán nhà biệt thự, liền kề Quận 9

Danh sách các dự án BĐS đã môi giới thành công: biệt thự Thảo Điền, khu Riviera An Phú, khu Riviera Cove Quận 9, khu Lake View An Phú Quận 2,...

City House Việt Nam mong muốn xây dựng một thương hiệu uy tín, đẳng cấp và là nơi khách hàng trao gửi niềm tin trọn vẹn.




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Townhouse for sale on 3/2 Street, District 10, near supermarket & bank, 39,9 billion, 8m x 18,5m

Townhouse for sale on 3/2 Street, District 10, HCMC Price: 39.9 billion VND, 8m x 18.5m, ground house + mezzanine + 3 floors. Rental price: 72.58 million VND Nice location; fast procedure; suitable for Business; near restaurants, supermarkets, schools, malls, etc. If you are inte...




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Senturia Central Point villa in Hi-Tech-Park District 9 for foreigners Great price great place

Hi-Tech Park is located on Xa Lo Hanoi, District 9.Only 12 km from the city center. Currently here, there are many domestic and foreign companies operating in the field of high technology from factory construction. And the most significant of which are: Nidec of Japan produces o...




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Townhouse, 126 sqm, Nguyen Huu Canh str, opposite to Sunwah Pearl - 3 mins drive to District 1

The location is extremely convenient for businessman, travellers, students, employees, who need to work/study/travel in the central districts, just 3 mins drive to district 1.The house has a nice view, located on Nguyen Huu Canh street near the corner of Ngo Tat To and Thu Thiem ...




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Selling Lavila Garden Town House Nguyen Huu Tho- Phuoc Kien- Nha Be Dist- 96.8 sqm-7.4 Billion

SELLING LAVILA GARDEN TOWNHOUSE ON NGUYEN HUU THO STREET- PHUOC KIEN WARD - NHA BE DISTRICT - Area : 5.5 x 17.6 m - Having a good location. - The house has 2 floors, is designed 4 large bedrooms - The sale price: 7.4 Billion Please do not hesitate to contact us via 0907894503 Mr....




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For Sale The Garden Townhouse Lavila Kien A- Nha Be District- 216.11sqm- The Negotiable Price

FOR SALE THE GARDEN TOWNHOUSE LAVILA KIEN A- NHA BE DISTRICT - Location: is the right facade of the main street, at the corner. - West- North direction - Land area: 8x17.6 m, corner: 136 sqm - Floor area: 216.11 sqm - Structure: a ground floor, 2 floors - Including 4 bedrooms, 5 ...




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Lucky House Kiến Hưng

Lucky House Kiến Hưng Hà Đông là dự án nhà ở xã hội do Công ty cổ phần Vinaconex21 làm chủ đầu tư. Dự án được khởi công xây dựng từ tháng 10/2016 và dự kiến sẽ hoàn thành trong quý III/2018.




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Phòng tắm của tương lai sẽ ra sao?

Từ gương thông minh cho phép con người đọc báo trong khi vệ sinh cá nhân, bồn tắm giúp làm giảm căng thẳng hay bồn cầu với tính năng sưởi ấm nắp ngồi... tất cả góp phần tạo nên phòng tắm tương lai tiện nghi, an toàn và thoải mái.




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Chàng trai 9x độc thân chia sẻ bí quyết kinh doanh, tậu nhà tiền tỷ

Sau 5 năm đi làm, chàng trai 9X ở Hà Tĩnh đã mua được một căn hộ chung cư rộng rãi tại Hà Nội với giá gần 2 tỷ đồng từ tiền tiết kiệm.




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Nhà phố thương mại - Shophouse

Shophouse (còn gọi là nhà phố thương mại) là mô hình nhà ở kiểu mới – nhà ở kết hợp với kinh doanh thương mại. Đây là hình thức bất động sản không mới trên thế giới, tuy mới xuất hiện tại thị trường bất động sản Việt Nam gần đây, Shophouse đã nhanh chóng tạo nên cơn sốt, cơn sóng đầu tư mạnh mẽ do có thiết kế thông minh, đa tính năng, vừa có thể kinh doanh vừa có thể để ở và cũng có thể cho thuê (shophouse for rent) để sinh lời.