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BRAF V600E-mutated metastatic pediatric Wilms tumor with complete response to targeted RAF/MEK inhibition [RESEARCH REPORT]

Wilms tumor (WT) is the most common renal malignancy of childhood and accounts for 6% of all childhood malignancies. With current therapies, the 5-yr overall survival (OS) for children with unilateral favorable histology WT is greater than 85%. The prognosis is worse, however, for the roughly 15% of patients who relapse, with only 50%–80% OS reported in those with recurrence. Herein, we describe the extended and detailed clinical course of a rare case of a child with recurrent, pulmonary metastatic, favorable histology WT harboring a BRAF V600E mutation. The BRAF V600E mutation, commonly found in melanoma and other cancers, and previously undescribed in WT, has recently been reported by our group in a subset of epithelial-predominant WT. This patient, who was included in that series, presented with unilateral, stage 1, favorable histology WT and was treated with standard chemotherapy. Following the completion of therapy, the patient relapsed with pulmonary metastatic disease, that then again recurred despite an initial response to salvage chemotherapy and radiation. Next-generation sequencing (NGS) on the metastatic pulmonary nodule revealed a BRAF V600E mutation. After weighing the therapeutic options, a novel approach with dual BRAF/MEK inhibitor combination therapy was initiated. Complete radiographic response was observed following 4 months of therapy with dabrafenib and trametinib. At 12 months following the start of BRAF/MEK combination treatment, the patient continues with a complete response and has experienced minimal treatment-related side effects. This represents the first case, to our knowledge, of effective treatment with BRAF/MEK molecularly targeted therapy in a pediatric Wilms tumor patient.




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A Case of Euglycemic Diabetic Ketoacidosis Triggered by a Ketogenic Diet in a Patient With Type 2 Diabetes Using a Sodium-Glucose Cotransporter 2 Inhibitor




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Diabetes Technologies: We Are All in This Together




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Distribution of Highly Prevalent Musculoskeletal Disorders and Their Association With Diabetes Complications in a Population of 140 Individuals With Type 1 Diabetes: A Retrospective Study in a French Diabetes Center

Although they are usually not considered to be diabetes complications, musculoskeletal disorders (MSKDs) are common in individuals with type 1 or type 2 diabetes and can strongly interfere with daily diabetes care, especially in people using diabetes technologies. The authors of this retrospective study in a population of 140 patients with type 1 diabetes report the distribution of subtypes of MSKDs and speculate about the mechanisms involved. The authors emphasize the need for multidisciplinary care involving not only the diabetes care team but also orthopedic surgeons. This report should lead to large, prospective studies to increase knowledge about these under-studied complications.




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Alcohol and Tobacco Use in Relation to Mammographic Density in 23,456 Women

Background:

Percent density (PD) is a strong risk factor for breast cancer that is potentially modifiable by lifestyle factors. PD is a composite of the dense (DA) and nondense (NDA) areas of a mammogram, representing predominantly fibroglandular or fatty tissues, respectively. Alcohol and tobacco use have been associated with increased breast cancer risk. However, their effects on mammographic density (MD) phenotypes are poorly understood.

Methods:

We examined associations of alcohol and tobacco use with PD, DA, and NDA in a population-based cohort of 23,456 women screened using full-field digital mammography machines manufactured by Hologic or General Electric. MD was measured using Cumulus. Machine-specific effects were estimated using linear regression, and combined using random effects meta-analysis.

Results:

Alcohol use was positively associated with PD (Ptrend = 0.01), unassociated with DA (Ptrend = 0.23), and inversely associated with NDA (Ptrend = 0.02) adjusting for age, body mass index, reproductive factors, physical activity, and family history of breast cancer. In contrast, tobacco use was inversely associated with PD (Ptrend = 0.0008), unassociated with DA (Ptrend = 0.93), and positively associated with NDA (Ptrend<0.0001). These trends were stronger in normal and overweight women than in obese women.

Conclusions:

These findings suggest that associations of alcohol and tobacco use with PD result more from their associations with NDA than DA.

Impact:

PD and NDA may mediate the association of alcohol drinking, but not tobacco smoking, with increased breast cancer risk. Further studies are needed to elucidate the modifiable lifestyle factors that influence breast tissue composition, and the important role of the fatty tissues on breast health.




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Pancreatic Cancer Risk in Relation to Lifetime Smoking Patterns, Tobacco Type, and Dose-Response Relationships

Background:

Despite smoking being a well-established risk factor for pancreatic cancer, there is a need to further characterize pancreatic cancer risk according to lifespan smoking patterns and other smoking features, such as tobacco type. Our aim was to deeply investigate them within a large European case–control study.

Methods:

Tobacco smoking habits and other relevant information were obtained from 2,009 cases and 1,532 controls recruited in the PanGenEU study using standardized tools. Multivariate logistic regression analysis was performed to evaluate pancreatic cancer risk by smoking characteristics and interactions with other pancreatic cancer risk factors. Fractional polynomials and restricted cubic splines were used to test for nonlinearity of the dose–response relationships and to analyze their shape.

Results:

Relative to never-smokers, current smokers [OR = 1.72; 95% confidence interval (95% CI), 1.39–2.12], those inhaling into the throat (OR = 1.48; 95% CI, 1.11–1.99) or chest (OR = 1.33; 95% CI, 1.12–1.58), and those using nonfiltered cigarettes (OR = 1.69; 95% CI, 1.10–2.61), were all at an increased pancreatic cancer risk. Pancreatic cancer risk was highest in current black tobacco smokers (OR = 2.09; 95% CI, 1.31–3.41), followed by blond tobacco smokers (OR = 1.43; 95% CI, 1.01–2.04). Childhood exposure to tobacco smoke relative to parental smoking was also associated with increased pancreatic cancer risk (OR = 1.24; 95% CI, 1.03–1.49). Dose–response relationships for smoking duration, intensity, cumulative dose, and smoking cessation were nonlinear and showed different shapes by tobacco type. Effect modification by family history of pancreatic cancer and diabetes was likely.

Conclusions:

This study reveals differences in pancreatic cancer risk by tobacco type and other habit characteristics, as well as nonlinear risk associations.

Impact:

This characterization of smoking-related pancreatic cancer risk profiles may help in defining pancreatic cancer high-risk populations.




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Harnessing Population Pedigree Data and Machine Learning Methods to Identify Patterns of Familial Bladder Cancer Risk

Background:

Relatives of patients with bladder cancer have been shown to be at increased risk for kidney, lung, thyroid, and cervical cancer after correcting for smoking-related behaviors that may concentrate in some families. We demonstrate a novel approach to simultaneously assess risks for multiple cancers to identify distinct multicancer configurations (multiple different cancer types that cluster in relatives) surrounding patients with familial bladder cancer.

Methods:

This study takes advantage of a unique population-level data resource, the Utah Population Database (UPDB), containing vast genealogy and statewide cancer data. Familial risk is measured using standardized incidence risk (SIR) ratios that account for sex, age, birth cohort, and person-years of the pedigree members.

Results:

We identify 1,023 families with a significantly higher bladder cancer rate than population controls (familial bladder cancer). Familial SIRs are then calculated across 25 cancer types, and a weighted Gower distance with K-medoids clustering is used to identify familial multicancer configurations (FMC). We found five FMCs, each exhibiting a different pattern of cancer aggregation. Of the 25 cancer types studied, kidney and prostate cancers were most commonly enriched in the familial bladder cancer clusters. Laryngeal, lung, stomach, acute lymphocytic leukemia, Hodgkin disease, soft-tissue carcinoma, esophageal, breast, lung, uterine, thyroid, and melanoma cancers were the other cancer types with increased incidence in familial bladder cancer families.

Conclusions:

This study identified five familial bladder cancer FMCs showing unique risk patterns for cancers of other organs, suggesting phenotypic heterogeneity familial bladder cancer.

Impact:

FMC configurations could permit better definitions of cancer phenotypes (subtypes or multicancer) for gene discovery and environmental risk factor studies.




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Selected Articles from This Issue




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Washing Buffer (0.1 M NaCl PBS)




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Adiposity Change Over the Life Course and Mammographic Breast Density in Postmenopausal Women

Mammographic breast density is a strong risk factor for breast cancer. We comprehensively investigated the associations of body mass index (BMI) change from ages 10, 18, and 30 to age at mammogram with mammographic breast density in postmenopausal women. We used multivariable linear regression models, adjusted for confounders, to investigate the associations of BMI change with volumetric percent density, dense volume, and nondense volume, assessed using Volpara in 367 women. At the time of mammogram, the mean age was 57.9 years. Compared with women who had a BMI gain of 0.1–5 kg/m2 from age 10, women who had a BMI gain of 5.1–10 kg/m2 had a 24.4% decrease [95% confidence interval (CI), 6.0%–39.2%] in volumetric percent density; women who had a BMI gain of 10.1–15 kg/m2 had a 46.1% decrease (95% CI, 33.0%–56.7%) in volumetric percent density; and women who had a BMI gain of >15 kg/m2 had a 56.5% decrease (95% CI, 46.0%–65.0%) in volumetric percent density. Similar, but slightly attenuated associations were observed for BMI gain from ages 18 and 30 to age at mammogram and volumetric percent density. BMI gain over the life course was positively associated with nondense volume, but not dense volume. We observed strong associations between BMI change over the life course and mammographic breast density. The inverse associations between early-life adiposity change and volumetric percent density suggest that childhood adiposity may confer long-term protection against postmenopausal breast cancer via its effect of mammographic breast density.




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NOX4 Inhibition Potentiates Immunotherapy by Overcoming Cancer-Associated Fibroblast-Mediated CD8 T-cell Exclusion from Tumors

Determining mechanisms of resistance to αPD-1/PD-L1 immune-checkpoint immunotherapy is key to developing new treatment strategies. Cancer-associated fibroblasts (CAF) have many tumor-promoting functions and promote immune evasion through multiple mechanisms, but as yet, no CAF-specific inhibitors are clinically available. Here we generated CAF-rich murine tumor models (TC1, MC38, and 4T1) to investigate how CAFs influence the immune microenvironment and affect response to different immunotherapy modalities [anticancer vaccination, TC1 (HPV E7 DNA vaccine), αPD-1, and MC38] and found that CAFs broadly suppressed response by specifically excluding CD8+ T cells from tumors (not CD4+ T cells or macrophages); CD8+ T-cell exclusion was similarly present in CAF-rich human tumors. RNA sequencing of CD8+ T cells from CAF-rich murine tumors and immunochemistry analysis of human tumors identified significant upregulation of CTLA-4 in the absence of other exhaustion markers; inhibiting CTLA-4 with a nondepleting antibody overcame the CD8+ T-cell exclusion effect without affecting Tregs. We then examined the potential for CAF targeting, focusing on the ROS-producing enzyme NOX4, which is upregulated by CAF in many human cancers, and compared this with TGFβ1 inhibition, a key regulator of the CAF phenotype. siRNA knockdown or pharmacologic inhibition [GKT137831 (Setanaxib)] of NOX4 “normalized” CAF to a quiescent phenotype and promoted intratumoral CD8+ T-cell infiltration, overcoming the exclusion effect; TGFβ1 inhibition could prevent, but not reverse, CAF differentiation. Finally, NOX4 inhibition restored immunotherapy response in CAF-rich tumors. These findings demonstrate that CAF-mediated immunotherapy resistance can be effectively overcome through NOX4 inhibition and could improve outcome in a broad range of cancers.Significance:NOX4 is critical for maintaining the immune-suppressive CAF phenotype in tumors. Pharmacologic inhibition of NOX4 potentiates immunotherapy by overcoming CAF-mediated CD8+ T-cell exclusion.Graphical Abstract:http://cancerres.aacrjournals.org/content/canres/80/9/1846/F1.large.jpg.See related commentary by Hayward, p. 1799




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Highlights from Recent Cancer Literature




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[PERSPECTIVES] Regulating Preimplantation Genetic Testing across the World: A Comparison of International Policy and Ethical Perspectives

Preimplantation genetic testing (PGT) is a reproductive technology that, in the course of in vitro fertilization (IVF), allows prospective parents to select their future offspring based on genetic characteristics. PGT could be seen as an exercise of reproductive liberty, thus potentially raising significant socioethical and legal controversy. In this review, we examine—from a comparative perspective—variations in policy approaches to the regulation of PGT. We draw on a sample of 19 countries (Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Israel, Italy, Japan, Mexico, Netherlands, Singapore, South Korea, Switzerland, United Kingdom, and the United States) to provide a global landscape of the spectrum of policy and legislative approaches (e.g., restrictive to permissive, public vs. private models). We also explore central socioethical and policy issues and contentious applications, including permissibility criteria (e.g., medical necessity), nonmedical sex selection, and reproductive tourism. Finally, we further outline genetic counseling requirements across policy approaches.




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Thalamic Massa Intermedia in Children with and without Midline Brain Malformations [PEDIATRICS]

BACKGROUND AND PURPOSE:

The massa intermedia is a normal midline transventricular thalamic connection. Massa intermedia aberrations are common in schizophrenia, Chiari II malformation, X-linked hydrocephalus, Cornelia de Lange syndrome, and diencephalic-mesencephalic junction dysplasia, among others. We have noticed that massa intermedia abnormalities often accompany other midline malformations. The massa intermedia has never been formally evaluated in a group of exclusively pediatric patients, to our knowledge. We sought to compare and contrast the prevalence, size, and location of the massa intermedia in pediatric patients with and without congenital midline brain abnormalities.

MATERIALS AND METHODS:

Successive 3T brain MR imaging examinations from pediatric patients with and without midline malformations were procured from the imaging data base at a pediatric hospital. Massa intermedia presence, size, morphology, and position were determined using 3D-TIWI with 1-mm isotropic resolution. The brain commissures, septum pellucidum, hypothalamus, hippocampus, vermis, and brain stem were evaluated to determine whether alterations were related to or predictive of massa intermedia abnormalities.

RESULTS:

The massa intermedia was more frequently absent, dysmorphic, and/or displaced in patients with additional midline abnormalities than in those without. The massa intermedia was absent in 40% of patients with midline malformations versus 12% of patients with normal findings (P < .001). Massa intermedia absence, surface area, and morphology were predictable by various attributes and alterations of the commissures, hippocampus, hypothalamus, vermis, brain stem, and third ventricle.

CONCLUSIONS:

Most pediatric patients have a thalamic massa intermedia centered in the anterior/superior third ventricle. Massa intermedia abnormalities are commonly associated with other midline malformations. Normal-variant massa intermedia absence is a diagnosis of exclusion.




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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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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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Is Histologic Thrombus Composition in Acute Stroke Linked to Stroke Etiology or to Interventional Parameters? [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Detailed insight into the composition of thrombi retrieved from patients with ischemic stroke by mechanical thrombectomy might improve pathophysiologic understanding and therapy. Thus, this study searched for links between histologic thrombus composition and stroke subtypes and mechanical thrombectomy results.

MATERIALS AND METHODS:

Thrombi from 85 patients who had undergone mechanical thrombectomy for acute ischemic stroke between December 2016 and March 2018 were studied retrospectively. Thrombi were examined histologically. Preinterventional imaging features, stroke subtypes, and interventional parameters were re-analyzed. Statistical analysis was performed with the Kruskal-Wallis test, Mann-Whitney U test, or Spearman correlation as appropriate.

RESULTS:

Cardioembolic thrombi had a higher percentage of macrophages and a tendency toward more platelets than thrombi of large-artery atherosclerotic stenosis (P = .021 and .003) or the embolic stroke of undetermined source (P = .037 and .099) subtype. Thrombi prone to fragmentation required the combined use of contact aspiration and stent retrieval (P = .021) and were associated with an increased number of retrieving maneuvers (P = .001), longer procedural times (P = .001), and a higher lymphocyte content (P = .035).

CONCLUSIONS:

We interpreted the higher macrophage and platelet content in cardioembolic thrombi compared with large-artery atherosclerotic stenosis or embolic stroke of undetermined source thrombi as an indication that the latter type might be derived from an atherosclerotic plaque rather than from an undetermined cardiac source. The extent of thrombus fragmentation was associated with a more challenging mechanical thrombectomy and a higher lymphocyte content of the thrombi. Thus, thrombus fragmentation not only might be caused by the recanalization procedure but also might be a feature of a lymphocyte-rich, difficult-to-retrieve subgroup of thrombi.




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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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Hippocampal Sclerosis Detection with NeuroQuant Compared with Neuroradiologists [FUNCTIONAL]

BACKGROUND AND PURPOSE:

NeuroQuant is an FDA-approved software that performs automated MR imaging quantitative volumetric analysis. This study aimed to compare the accuracy of NeuroQuant analysis with visual MR imaging analysis by neuroradiologists with expertise in epilepsy in identifying hippocampal sclerosis.

MATERIALS AND METHODS:

We reviewed 144 adult patients who underwent presurgical evaluation for temporal lobe epilepsy. The reference standard for hippocampal sclerosis was defined by having hippocampal sclerosis on pathology (n = 61) or not having hippocampal sclerosis on pathology (n = 83). Sensitivities, specificities, positive predictive values, and negative predictive values were compared between NeuroQuant analysis and visual MR imaging analysis by using a McNemar paired test of proportions and the Bayes theorem.

RESULTS:

NeuroQuant analysis had a similar specificity to neuroradiologist visual MR imaging analysis (90.4% versus 91.6%; P = .99) but a lower sensitivity (69.0% versus 93.0%, P < .001). The positive predictive value of NeuroQuant analysis was comparable with visual MR imaging analysis (84.0% versus 89.1%), whereas the negative predictive value was not comparable (79.8% versus 95.0%).

CONCLUSIONS:

Visual MR imaging analysis by a neuroradiologist with expertise in epilepsy had a higher sensitivity than did NeuroQuant analysis, likely due to the inability of NeuroQuant to evaluate changes in hippocampal T2 signal or architecture. Given that there was no significant difference in specificity between NeuroQuant analysis and visual MR imaging analysis, NeuroQuant can be a valuable tool when the results are positive, particularly in centers that lack neuroradiologists with expertise in epilepsy, to help identify and refer candidates for temporal lobe epilepsy resection. In contrast, a negative test could justify a case referral for further evaluation to ensure that false-negatives are detected.




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Authorship Trends in the American Journal of Neuroradiology [LETTERS]




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Chính chủ bán lỗ kiot khu đô thị Thanh hà tòa HH03F nằm ngay đầu hồi. LH 0913025373

Chính chủ cần bán kiot khu đô thị Thanh Hà Tòa HH03F. - Diện tích 36,69 m2. - Thuộc căn kiot quay mặt ra sân chơi và đường 25m, lối vào công viên và hồ. - Nằm ngay cửa sảnh đi ra đi vào của cư dân. Nằm ngay đầu hồi. Đang cho thuê ổn định. - Giá bán: Thỏa thuận (có thương lượng ch...




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Bán shop office, kiot chân khối đế mặt đường Hàm Nghi, Vinhomes Gardenia. LH 0983786378

Bán shop office Vinhomes Gardenia, bán shop chân khối đế mặt Hàm Nghi 3 tòa chung cư A1, A2, A3 Vinhomes Gardenia Mỹ Đình, Nam từ Liêm. Bán kiot mặt Hàm nghi Gardenia. 1. Shop Diện tích 112.8 m2. Đang cho thuê 100 triệu/th, hợp đồng thuê còn 5 năm, thanh toán 12 tháng/ lần....




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Chuyên cho thuê căn hộ Hà Đô Centrosa Garden 1,2,3PN giá tốt nhất thị trường. LH 0901693299

Xin chào quý anh/chị, với giỏ hàng phong phú và đa dang của chúng tôi bao gồm các loại căn hộ 1PN, 1PN + 1, 2PN, 2PN + 1, 3PN chắc chắn anh/chị sẽ lựa chọn được cho mình căn hộ phù hợp nhất.* Liên hệ ngay: 0901.693.299 Mr: Nghệ - để được tư vấn và hỗ trợ.* Báo giá cho thuê căn hộ...




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Cho thuê căn hộ Vinhomes Ba Son Quận 1 với giá tốt nhất thị trường, liên hệ ngay 0901698818

Phòng kinh doanh chuyên cho thuê căn hộ Officetel, 1PN, 2PN, 3PN, 4PN, penthouse Vinhomes Golden River Ba Son. Giá tốt nhất thị trường.Liên hệ: 0901698818 (Quốc Cường).Nhận ký gửi cho thuê, chuyển nhượng dự án Vinhomes Golden River Ba Son và các dự án lân cận. * Xin gửi anh/chị g...




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Sunshine Wonder Villas

Sunshine Wonder Villas là dự án nằm trong chuỗi biệt thự mang thương hiệu Sunshine Villas của Tập đoàn Sunshine, được ra đời nhằm kiến tạo nên một không gian sống đậm chất sinh thái, nghỉ dưỡng đẳng cấp bậc nhất Thủ đô.




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Khu đô thị Phương Đông

Khu đô thị Phương Đông là khu phức hợp nằm ngay cửa ngõ đặc khu kinh tế Vân Đồn với 200 lô biệt thự đơn lập, song lập cùng 500 lô liền kề và shophouse.




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Khu đô thị sinh thái biển AE Resort

AE Resort là dự án phức hợp nghỉ dưỡng quy mô lớn đầu tiên tại Quảng Trị, có quy mô 36,115ha, được đầu tư bởi Công ty CP Tập đoàn AE.




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Công ty CP Đầu tư Tài chính Thiên Việt




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Charm city căn hộ Chuẩn resort sở hữu Vincom đầu tiên tại Bình Dương, Pháp Lý Hoàn Chỉnh.1.5 tỷ/căn

- Chiết khấu 1% khi khách hàng booking trước ngày mở bán. - Tặng 2 chỉ vàng khi khách sở hữu căn hộ. - Chiết khấu ưu đãi thanh toán từ 3 - 5%. Và nhiều giá trị ưu đãi vào ngày sự kiện hàng tuần và mở bán. Charm city dự án khu phức hợp căn hộ, thương mại, giải trí trung tâm TP...




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Còn 6 ngày! Thanh toán 18%/9 tháng+ CK 18%+ hoàn 5%+bảo hiểm 400tr khi mua căn hộ trung tâm TP biển

Thân chào quý anh/ chị. Hiện em đang có 1 căn hàng chủ đầu tư 2 phòng ngủ, 2 WC (68,9m2) cực thoáng mát view biển, tầng trung, hướng Đông Bắc giá chỉ 36,9 triệu/m2 (2.580 tỷ) hiện đang được chiết khấu chỉ còn 1.609 tỷ ( tương đương 24,6 tr/m2). Cụ thể: + Chiết khấu nội bộ 6%/ giá trị căn: Giảm ngay 154,8 triệu. + Hoàn lại 5%/ giá trị thanh toán: Tương ứng 100,6 triệu. + ...




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CHUYÊN chuyển nhượng Masteri giá thật đang có 2PN view hồ bơi giá chỉ 3,3 tỷ. LH em Ni 0901381558

Em chuyên giỏ hàng Masteri Thảo Điền và Masteri An Phú. Giá và vị trí căn hộ nào cũng có hàng. * Có mặt ở Masteri 24/7 để dẫn khách hàng đi xem thực tế căn hộ đã bàn giao, những căn hộ đã có nội thất đầy đủ. * Sổ hồng pháp lý rõ ràng, hỗ trợ vay ngân hàng lên tới 80% giá trị căn hộ. * Cam kết tư vấn đúng nhu cầu, đúng sự thật. Trước khi mua Masteri, muốn tìm hiểu tốt n...




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Chính chủ bán gấp mặt bằng kinh doanh tại chung cư Athena Complex rẻ hơn giá thị trường 200tr

- Chính chủ cần tiền bán gấp mặt bằng kinh doanh tại chung cư Athena Complex Trần Hữu Dực, giá chỉ 18.5tr/m2, rẻ hơn thị trường 200tr, LH: 0973705081. - Hiện có thể cho thuê lại với giá từ 18 - 25tr/ tháng. - Sổ đỏ chính chủ. - DT: 100m2.I, Tổng quan dự án Athena Complex. Tên dự ...




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Bán gấp CH Vista Verde 3PN 130m2 view hồ bơi, giá chỉ 5.4 tỷ, 4PN tháp Lotus 212m2 view sông 9.8 tỷ

* Căn mới, duy nhất chỉ một căn, chủ nhà cần bán gấp. - Tháp T2, tầng trung, 3 phòng ngủ, 2WC, ban công rộng. - Diện tích: 130m2. - Decor full nội thất cao cấp phong cách Châu Âu, cực kỳ sang trọng. - Hướng cửa: Đông Nam. Ban công: Tây Bắc, View trọn vẹn hồ bơi nội khu đẹp lung l...




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Nhanh tay sở hữu căn hộ Bcons Green View cực đẹp, giá gốc CĐT, đối diện Big C Dĩ An TT chỉ 10%

Liên hệ: 0933 686 500.Hiện đang nhận booking ưu tiên Giai đoạn 2.Căn đẹp tầng đẹp.Giá gốc từ chủ đầu tư.Chỉ từ 1 tỷ 3 ~ 1 tỷ 5/ căn 2 PN (thanh toán chỉ 130tr~140tr).Thông tin:Tên dự án: Căn hộ Bcons Green View.Nối tiếp hàng loạt dự án hot vượt tiến độ tại Dĩ An. Bcons Suối Tiên ...




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Căn hộ TT thành phố Dĩ An ngay cửa ngõ Sài Gòn chỉ cần thanh toán trước chỉ 10% cho căn 2PN, 43m2

Kính chào quý khách hàng! Dự án căn hộ Bcons Green View thành phố Dĩ An mặt tiền QL1K + Chỉ từ 1 tỷ 371 / căn 2PN 1WC 43m2.- Thanh toán đợt đầu chỉ 10% giá chưa VAT (Phương thức thanh toán linh hoạt góp trong 2 năm). - Chỉ từ 130 triệu có thể sở hữu ngay căn hộ Bcons Green View (...




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Chuyên chuyển nhượng CH Masteri Thảo Điền giá rẻ nhất thị trường hỗ trợ vay 80%. LH 0906574444 Dung

Liên hệ ngay để được hướng dẫn chọn căn nhà vừa ý nhất 0906.57.4444 gặp Dung (24/7). Ở đâu giá rẻ, em có giá rẻ hơn. Hỗ trợ tư vấn nhiệt tình + tận tâm + lấy uy tín làm đầu + không mua cũng không sao. Bên em cam kết: Giá rẻ hơn thị trường, trả sát giá chủ nhà. Miễn sao k...




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Vũng Tàu Pearl - Chiết Khấu Khủng Hotline: 0932.868.472

Vũng Tàu Pearl - Chiết Khấu Khủng - Chiết khấu ngay 7% - 10% cho quý Khách Hàng là những Y - Bác sĩ trên cả nước. Những người chiến sĩ áo trắng nơi tuyến đầu chống dịch. - Chiết khấu 4% - 6% cho quý Khách Hàng ngoài ngành y. - Chiết khấu 5% giá trị thanh toán cho tất cả các lầ...




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CĂN HỘ GRAND CENTER QUY NHƠN CK KHỦNG LÊN ĐẾN 900TR/CĂN CHỈ CÒN 1.5TỶ/CĂN 2PN LH: 0907 810 870

Chiết khấu cực khủng 30 - 40% từ cđt hưng thịnh, mua căn 1.9 tỷ giảm còn 1.1 tỷ.Sở hữu vị trí vàng 01 Nguyễn Tất Thành Thành phố Quy Nhơn với 4 mặt tiền đường, 3 mặt view biển và 1 mặt view hồ Bầu Sen, CDT Hưng Thịnh trân trọng gửi tới quý KH dự án căn hộ Smarthome đầu tiên tại t...




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Đất phân lô cách Trôi 1km, sát khu đô thị diện tích 54m2, vỉa hè thoáng, giá 2.43 tỷ

Đất phân lô cách Trôi 1km, sát khu đô thị diện tích 54m2, vỉa hè thoáng, giá 2.43 tỷ. Đường trước đất rộng rãi, chia ô bàn cờ đi lại thuận tiện. Kết nối dễ dàng với Quốc Lộ 32. Trong khu đô thị Tân Tây Đô rất nhiều tiện ích. Kích thước đất xây nhà rất đẹp, mặt tiền 4.5m. Giá bán ...




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Bán suất đất nền ngoại giao trung tâm thị xã Mỹ Hào - Hưng Yên 87m2 giá 19tr/m2 MT 5m: 0983142869

Tên dự án: Khu đô thị Yên Sơn. Chủ đầu tư: Hợp tác đầu tư giữa Công ty CP Yên Sơn và Công ty TNHH Công Nghiệp Thực Phẩm Quốc Tế, trong đó Công ty CP Yên Sơn đứng tên trên hồ sơ Dự án. Mật độ xây dựng: 53,4%. Diện tích, quy mô dự án: 17,2 hecta. Khu đô thị với đầu đủ tiện ích.Diện...




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Đất nền nhà phố liền kề đường Tô Hiệu, Tân Phú. Giá chỉ từ 5 tỷ 9

Siêu phẩm nền nhà phố đường Tô Hiệu, Quận Tân Phú. Hoà Bình City. Tổng diện tích khu đất: 6700m2. Tổng nền đất phân lô: 76 nền nhà phố sổ hồng riêng (thổ cư 100%).Diện tích đa dạng: 5x15m - 5x17m - 4x15m - 4x17m - 8x17m. Đã được cấp có sổ hồng riêng tháng 8/2019. Với cơ sở hạ tần...




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Chính thức nhận đặt chỗ siêu phẩm liền kề đại học Việt Đức, chỉ với 599tr, trả góp 0% lãi, sổ riêng

* Chính thức mở bán siêu phẩm liền kề đại học quốc tế Việt Đức. - Cơ hội an cư & đầu tư hấp dẫn tại khu đô thị phức hợp đầu tiên tại Bình Dương. * Đặc biệt, động thổ công viên trung tâm tại dự án với nhiều chương trình hấp dẫn. - Điểm tham quan du lịch lý tưởng cuối tuần. - Đất n...