DWI-Based Algorithm to Predict Disability in Patients Treated with Thrombectomy for Acute Stroke.

BACKGROUND AND PURPOSE: The reasons for poor clinical outcome after thrombectomy for acute stroke, concerning around half of all patients, are misunderstood. We developed a hierarchic algorithm based on DWI to better identify patients at high risk of disability. MATERIALS AND METHODS: Our single-center, retrospective study included consecutive patients with acute ischemic stroke who underwent thrombectomy for large anterior artery occlusion and underwent pretreatment DWI. The primary outcome was the mRS at 3 months after stroke onset. Multivariable regression was used to identify independent clinical and imaging predictors of poor prognosis (mRS > 2) at 3 months, and a hierarchic algorithm predictive of disability was developed. RESULTS: A total of 149 patients were analyzed. In decreasing importance, DWI lesion volume of >80 mL, baseline NIHSS score of >14, age older than 75 years, and time from stroke onset to groin puncture of >4 hours were independent predictors of poor prognosis. The predictive hierarchic algorithm developed from the multivariate analysis predicted the risk of disability at 3 months for up to 100% of patients with a high predictive value. The area under the receiver operating characteristic curve was 0.87. CONCLUSIONS: The DWI-based hierarchic algorithm we developed is highly predictive of disability at 3 months after thrombectomy and is easy to use in routine practice.

Cost-effectiveness of five prenatal screening strategies for trisomies and other unbalanced chromosomal abnormalities: model-based analysis.

OBJECTIVE: To evaluate the cost-effectiveness of five prenatal screening strategies for trisomies (13/18/21) and other unbalanced chromosomal abnormalities (UBCA), following the introduction of cell-free DNA (cfDNA) analysis. METHODS: A model-based cost-effectiveness analysis was performed to estimate prevalence, safety, screening-program costs and healthcare costs of five different prenatal screening strategies, using a virtual cohort of 652 653 pregnant women in France. Data were derived from the French Biomedicine Agency and published articles. Uncertainty was addressed using one-way sensitivity analysis. The five strategies compared were: (i) cfDNA testing for women with a risk following first-trimester screening of ≥ 1/250; (ii) cfDNA testing for women with a risk of ≥ 1/1000 (currently recommended); (iii) cfDNA testing in the general population (regardless of risk); (iv) invasive testing for women with a risk of ≥ 1/250 (historical strategy); and (v) invasive testing for women with a risk of ≥ 1/1000. RESULTS: In our virtual population, at similar risk thresholds, cfDNA testing compared with invasive testing was cheaper but less effective. Compared with the historical strategy, cfDNA testing at the ≥ 1/1000 risk threshold was a more expensive strategy that detected 158 additional trisomies, but also 175 fewer other UBCA. Implementation of cfDNA testing in the general population would give an incremental cost-effectiveness ratio of €9 166 689 per additional anomaly detected compared with the historical strategy. CONCLUSION: Extending cfDNA to lower risk thresholds or even to all pregnancies would detect more trisomies, but at greater expense and with lower detection rate of other UBCA, compared with the historical strategy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Relación costo-eficacia de cinco estrategias de cribado prenatal para trisomías y otras anomalías cromosómicas no equilibradas: un análisis basado en modelos OBJETIVO: Evaluar la eficacia en función de los costos de cinco estrategias de cribado prenatal para trisomías (13/18/21) y otras anomalías cromosómicas no equilibradas (UBCA, por sus siglas en inglés), tras la introducción del análisis de ADN fetal (cfDNA, por sus siglas en inglés). MÉTODOS: Se realizó un análisis de la relación costo-eficacia basado en modelos para estimar la prevalencia, la seguridad, los costos de los programas de cribado y los costos sanitarios de cinco estrategias diferentes de cribado prenatal, para lo cual se usó una cohorte virtual de 652 653 mujeres embarazadas en Francia. Los datos se obtuvieron de la Agencia Francesa de Biomedicina y de artículos publicados. La incertidumbre se abordó mediante un análisis de sensibilidad unidireccional. Las cinco estrategias comparadas fueron: (i) pruebas de cfDNA para mujeres con un riesgo ≥1/250 después del examen del primer trimestre; (ii) pruebas de cfDNA para mujeres con un riesgo ≥1/1000 (las recomendadas actualmente); (iii) pruebas de cfDNA en la población general (independientemente del riesgo); (iv) pruebas invasivas para mujeres con un riesgo ≥1/250 (estrategia histórica); y (v) pruebas invasivas para mujeres con un riesgo ≥1/1000. RESULTADOS: En esta población virtual, con umbrales de riesgo similares, la prueba de cfDNA fue más barata pero menos efectiva en comparación con la prueba invasiva. En comparación con la estrategia histórica, la prueba de cfDNA para el umbral de riesgo de ≥1/1000 fue una estrategia más costosa que detectó 158 trisomías adicionales, pero también 175 menos de otras UBCA. La aplicación de las pruebas de cfDNA en la población general daría una relación costo-eficacia incremental de 9 166 689 EUR por cada anomalía adicional detectada en comparación con la estrategia histórica. CONCLUSIÓN: Extender las pruebas de cfDNA a umbrales de riesgo más bajos o incluso a todos los embarazos detectaría más trisomías, pero a un costo mayor y con una tasa de detección más baja de otras UBCA, en comparación con la estrategia histórica.

Optimal MRI sequence for identifying occlusion location in acute stroke: which value of time-resolved contrast-enhanced MRA?

BACKGROUND AND PURPOSE: Identifying occlusion location is crucial for determining the optimal therapeutic strategy during the acute phase of ischemic stroke. The purpose of this study was to assess the diagnostic efficacy of MR imaging, including conventional sequences plus time-resolved contrast-enhanced MRA in comparison with DSA for identifying arterial occlusion location. MATERIALS AND METHODS: Thirty-two patients with 34 occlusion levels referred for thrombectomy during acute cerebral stroke events were consecutively included from August 2010 to December 2012. Before thrombectomy, we performed 3T MR imaging, including conventional 3D-TOF and gradient-echo T2 sequences, along with time-resolved contrast-enhanced MRA of the extra- and intracranial arteries. The 3D-TOF, gradient-echo T2, and time-resolved contrast-enhanced MRA results were consensually assessed by 2 neuroradiologists and compared with prethrombectomy DSA results in terms of occlusion location. The Wilcoxon test was used for statistical analysis to compare MR imaging sequences with DSA, and the κ coefficient was used to determine intermodality agreement. RESULTS: The occlusion level on the 3D-TOF and gradient-echo T2 images differed significantly from that of DSA (P < .001 and P = .002, respectively), while no significant difference was observed between DSA and time-resolved contrast-enhanced MRA (P = .125). κ coefficients for intermodality agreement with DSA (95% CI, percentage agreement) were 0.43 (0.3%-0.6; 62%), 0.32 (0.2%-0.5; 56%), and 0.81 (0.6%-1.0; 88%) for 3D-TOF, gradient-echo T2, and time-resolved contrast-enhanced MRA, respectively. CONCLUSIONS: The time-resolved contrast-enhanced MRA sequence proved reliable for identifying occlusion location in acute stroke with performance superior to that of 3D-TOF and gradient-echo T2 sequences.

Rad54 is required for the normal development of male and female germ cells and contributes to the maintainance of their genome integrity after genotoxic stress.

Rad54 is an important factor in the homologous recombination pathway of DNA double-strand break repair. However, Rad54 knockout (KO) mice do not exhibit overt phenotypes at adulthood, even when exposed to radiation. In this study, we show that in Rad54 KO mouse the germline is actually altered. Compared with the wild-type (WT) animals, these mice have less premeiotic germ cells. This germ cell loss is found as early as in E11.5 embryos, suggesting an early failure during mutant primordial germ cells development. Both testicular and ovarian KO germ cells exhibited high radiation sensitivity leading to a long-term gametogenesis defect at adulthood. The KO female germline was particularly affected displaying decreased litter size or sterility. Spermatogenesis recovery after irradiation was slower and incomplete in Rad54 KO mice compared with that of WT mice, suggesting that loss of germ stem cell precursors is not fully compensated along the successive rounds of spermatogenesis. Finally, spermatogenesis recovery after postnatal irradiation is in part regulated by glial-cell-line-derived neurotrophic factor (GDNF) in KO but not in irradiated WT mice, suggesting that Sertoli cell GDNF production is stimulated upon substantial germ cell loss only. Our findings suggest that Rad54 has a key function in maintaining genomic integrity of the developing germ cells.

[Validation of a clinical prediction rule for the diagnosis of deep vein thrombosis of the lower limbs in primary care]. / Validation d'un score de prédiction clinique de la thrombose veineuse profonde des membres inférieurs spécifique à la médecine générale.

PURPOSE: Patients with suspected deep vein thrombosis (DVT) are often managed on an outpatient basis. The aim of the study was to validate a clinical prediction rule specifically for use in primary care to help physicians in their decision to start anticoagulant therapy while awaiting ultrasound examination. PATIENTS AND METHODS: Between September 2007 and October 2008, 194 general practitioners prospectively included patients with clinically suspected DVT without clinically suspected pulmonary embolism. All patients underwent a standardized clinical assessment in order to collect items included in the clinical prediction rule (personal history of venous thromboembolism +1, immobilization in previous month+1, estrogen contraceptive+2, active malignancy+3, swelling of the calf+1, the presence of an alternative diagnosis more likely than that of DVT-3. DVT unlikely if score<2, likely if score≥2). RESULTS: Among the 164 included patients, 56 (34%) had DVT of them 28 (17%) had a proximal DVT. Proportions of confirmed DVT were 29% in the unlikely group and 43% in the likely group against 26% and 63% respectively in the derivation study. CONCLUSIONS: This clinical prediction rule might not fulfill the required conditions to be considered as a usable help in the ambulatory management of DVT. Variations of the cut-off value could enhance its performance.

HIF-2alpha specifically activates the VE-cadherin promoter independently of hypoxia and in synergy with Ets-1 through two essential ETS-binding sites.

The mechanisms that are responsible for the restricted pattern of expression of the VE-cadherin gene in endothelial cells are not clearly understood. Regulation of expression is under the control of an approximately 140 bp proximal promoter that provides basal, non-endothelial specific expression. A larger region contained within the 2.5 kb genomic DNA sequence located ahead of the transcription start is involved in the specific expression of the gene in endothelial cells. We show here that the VE-cadherin promoter contains several putative hypoxia response elements (HRE) which are able to bind endothelial nuclear factors under normoxia. The VE-cadherin gene is not responsive to hypoxia but hypoxia-inducible factor (HIF)-2alpha specifically activates the promoter while HIF-1alpha does not. The HRE, that are involved in this activity have been identified. Further, we show that HIF-2alpha cooperates with the Ets-1 transcription factor for activation of the VE-cadherin promoter and that this synergy is dependent on the binding of Ets-1 to DNA. This cooperative action of HIF-2alpha with Ets-1 most probably participates to the transcriptional regulation of expression of the gene in endothelial cells. This mechanism may also be involved in the expression of the VE-cadherin gene by tumor cells in the process of vascular mimicry.

Volumetric quantitative computed tomography of the proximal femur: relationships linking geometric and densitometric variables to bone strength. Role for compact bone.

INTRODUCTION: In assessing cervical fractures of the proximal femur, this in vitro quantitative computed tomography (QCT) study had three objectives: to compare QCT to dual-energy X-ray absorptiometry (DXA) for predicting the failure load of the proximal femur, to compare the contributions of density and geometry to bone failure load, and to compare the contributions of cortical and trabecular bone to bone failure load. A novel three-dimensional (3D) analysis tool [medical image analysis framework (MIAF-Femur)] was used to analyze QCT scans. METHODS: The proximal ends of 28 excised femurs were studied (1) using QCT to separately measure bone mineral density (BMD) and geometric variables of trabecular and cortical bone, (2) using mechanical tests to failure in a stance configuration, and (3) using DXA to measure BMD. The variables were described with mean, standard deviation, and range. Correlation matrix and multivariate linear models were computed. RESULTS: Among correlations, cortical thicknesses of the femoral neck were significantly correlated with femoral failure load, especially of the inferoanterior quadrant (r2=0.41; p<0.001), as was cortical volume at the "extended neck" (r2=0.41; p<0.001). Femoral failure load variance was best explained by a combination of QCT variables. Combining densitometric and geometric variables measured by QCT explained 76% of femoral failure load variance compared with 69% with the DXA model. Geometric variables (measured by QCT) explained 43% of femoral failure load variance compared with 72% for densitometric variables (measured by QCT). A model including only trabecular variables explained 52% of femoral failure load variance compared with 59% for a model including only cortical variables. CONCLUSION: The QCT-MIAF reported here provides analysis of both geometric and densitometric variables characterizing cortical and trabecular bone. Confirmation of our results in an independent sample would suggest that QCT may better explain failure load variance for cervical fracture than the gold standard DXA-provided BMD.

Three-dimensional X-ray absorptiometry (3D-XA): a method for reconstruction of human bones using a dual X-ray absorptiometry device.

Three-dimensional accurate evaluation of the geometry of the proximal femur may be helpful for hip fracture risk evaluation. The purpose of this study was to apply and validate a stereo-radiographic 3D reconstruction method of the proximal femur, using contours identification from biplanar DXA images. Twenty-five excised human proximal femurs were investigated using a standard DXA unit. Three-dimensional personalized models were reconstructed using a dedicated non-stereo corresponding contours (NSCC) algorithm. Three-dimensional CT-scan reconstructions obtained on a clinical CT-scan unit were defined as geometric references for the comparison protocol, in order to assess accuracy and reproducibility of the 3D stereo-radiographic reconstructions. The precision of a set of 3D geometric parameters (femoral-neck axis length, mid-neck cross-section area, neck-shaft angle), obtained from stereo-radiographic models was also evaluated. This study shows that the NSCC method may be applied to obtain 3D reconstruction from biplanar DXA acquisitions. Applied to the proximal femur, this method showed good accuracy as compared with high-resolution personalized CT-scan models (mean error = 0.8 mm). Moreover, precision study for the set of 3D parameters yielded coefficients of variation lower than 5%. This is the first study providing 3D geometric parameters from standard 2D DXA images using the NSCC method. It has good accuracy and reproducibility in the present study on cadaveric femurs. In vivo prospective studies are needed to evaluate its discriminating potential on hip fracture risk prediction.

Validation of the relative 3D orientation of vertebrae reconstructed by bi-planar radiography.

The three dimensional (3D) reconstruction of the spine can be obtained by stereoradiographic techniques. To be safely used on a routine clinics basis, stereoradiography must provide both accurate vertebral shape and coherent position. Although the accuracy of the reconstructed morphology of the vertebrae is well documented, only few authors studied the accuracy of the vertebral orientation. Therefore, this paper focuses on the evaluation of the orientation accuracy of the reconstructed vertebrae (obtained by non-stereo corresponding point technique) considering either a 178 point vertebral model or a 6 point vertebral model (previously proposed in the literature). Five dried vertebrae were fixed on holders containing four markers each. The 3D reconstruction of both vertebrae and markers were obtained by stereoradiographic techniques. Using least square method matching from one position to another, the relative orientation was computed for the vertebral models (6 or 178 points) and the four markers. These vertebral and holder orientations were compared (considering the holder's one as reference). The repeatability of these relative orientations (vertebrae and holders) was also evaluated. The mean (RMS) orientation error of 178 point vertebral model was 0.6 degrees (0.8 degrees ), for lateral rotation, 0.7 degrees (1.0 degrees ) for sagittal rotation and 1.4 degrees (1.9 degrees ) for axial rotation. The intra-observer repeatability was 0.5 degrees (0.7 degrees ) for lateral rotation, 0.7 degrees (0.8 degrees ) for sagittal rotation and 0.9 degrees (1.2 degrees ) for axial rotation. The orientation was found more accurate and precise when using the 178 point vertebral model than when using the basic 6 point vertebral model. The relative orientation (in post-operative follow-up with respect to the pre-operative examination) of the vertebrae of one scoliotic patient was performed as an example of clinical application. The stereoradiographic method is a reliable 3D quantitative tool to assess the spine deformity, that can be used in clinics for the follow-up of scoliotic patients.

3D reconstruction of the proximal femur with low-dose digital stereoradiography.

OBJECTIVE: Accurate three-dimensional (3D) geometry of the proximal femur may be helpful for fracture risk evaluation, as well as for planning and assisting surgical procedures. The purpose of this study was to apply and validate a stereoradiographic 3D reconstruction method on the proximal femur from radiographic contours identified on bi-planar radiographs. MATERIALS AND METHODS: Twenty-five excised non-pathologic proximal femurs were investigated using a low-dose digital radiographic device. Three-dimensional personalized models were reconstructed using the Non-Stereo Corresponding Contours (NSCC) algorithm. Three-dimensional CT-scan reconstructions were defined as geometric references for the comparison protocol, in order to assess the accuracy and reproducibility of the personalized 3D stereoradiographic reconstructions. In addition, the reliability of a set of 3D parameters obtained from stereoradiographic models was evaluated. RESULTS: This study demonstrated the validity of the NSCC method when applied to the proximal femur, with good results for accuracy (mean error = 0.7 mm) and reproducibility (Wilcoxon test: p > 0.28). Moreover, a precision study for the set of 3D parameters yielded a coefficient of variation lower than 5%. CONCLUSIONS: Once this approach has been validated in vivo, it should find multiple applications in therapeutic fields (e.g., for surgical planning, computer assisted surgery, etc.), as well as in diagnostic contexts (e.g., equilibrium studies or osteoporosis fracture risk assessment).

3D detailed reconstruction of vertebrae with low dose digital stereoradiography.

As scoliosis requires a global and local 3D examination of the spine in standing position, stereoradiography appears as one of the most adequate 3D imaging tool for it diagnosis. Our purpose was to increase the geometry definition of the stereoradiographic reconstruction to obtain morpho-realistic models and to validate them using 41 dry vertebrae. Our results propose 2000 points 3D personalised models without any loss of accuracy in comparison to previous studies.

[Diffuse leiomyomatosis with genital involvement and Alport syndrome. Report of two cases]. / Léiomyomatose diffuse avec atteinte génitale et syndrome d'Alport. A propos de deux cas.

We observed the cases of two young women who both developed esophageal and perineal tumors successively. The esophageal component usually is the first manifestation. Esophagectomy, with or without gastrectomy is generally required. The genital affection involves the periclitoridian region, the minora and majora labia. Tracheobronchial localization is less common, but it may be lethal due to bronchospasm. An association between diffuse leiomyomatosis and Alport syndrome is not fortuitous. Recently, molecular biology has enabled to understand the combination of the two pathologies by showing the presence of a deletion on adjacent X chromosome genes, COL4A5 and COL4A6, which are involved in the synthesis of type IV collagen fibres. Leiomyomatosis and Alport syndrome are transmitted as X-linked dominant traits. Women with diffuse leiomyomatosis transmit Alport syndrome. An antenatal diagnosis can be proposed for such patients.