Slc20a2, Encoding the Phosphate Transporter PiT2, Is an Important Genetic Determinant of Bone Quality and Strength.

Osteoporosis is characterized by low bone mineral density (BMD) and fragility fracture and affects over 200 million people worldwide. Bone quality describes the material properties that contribute to strength independently of BMD, and its quantitative analysis is a major priority in osteoporosis research. Tissue mineralization is a fundamental process requiring calcium and phosphate transporters. Here we identify impaired bone quality and strength in Slc20a2-/- mice lacking the phosphate transporter SLC20A2. Juveniles had abnormal endochondral and intramembranous ossification, decreased mineral accrual, and short stature. Adults exhibited only small reductions in bone mass and mineralization but a profound impairment of bone strength. Bone quality was severely impaired in Slc20a2-/- mice: yield load (-2.3 SD), maximum load (-1.7 SD), and stiffness (-2.7 SD) were all below values predicted from their bone mineral content as determined in a cohort of 320 wild-type controls. These studies identify Slc20a2 as a physiological regulator of tissue mineralization and highlight its critical role in the determination of bone quality and strength. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc

Le Lipiocis® dans le traitement du carcinome hépatocellulaire (étude rétrospective)

BUT : L'objectif principal de cette étude est l'évaluation de l'efficacité du traitement par le Lipiocis® dans le carcinome hépatocellulaire au stade avancé avec ou sans thrombose portale. Puis de corréler cette survie aux paramètres clinico-biologiques et de rechercher les complications précoces et tardives. MATERIELS ET METHODES : Il s'agit d une étude rétrospective réalisée au CHU de Nantes sur 50 patients traités par le Lipiocis® de novembre 2002 à juin 2009, comparée au groupe témoin de 36 patients ayant les mêmes caractéristiques cliniques. RESULTATS : Pour le groupe Lipiocis® la médiane de la survie est de 32 semaines, soit 224 jours. La survie globale est de 90% à 3 mois, 65% à 6 mois, 45% à 9 mois, 35% à 1 an, 22% à 2 ans, 6% à 3 ans et 1% à 5 ans. Pour le groupe témoin la médiane de survie est de 8 semaines, soit 56 jours et la survie globale est de 47% à 3 mois, 28% à 6 mois, 10% à 9 mois, 8% à 1 an et 0% à 2 ans. Le gain de survie est statistiquement significatif (p=0,007). La tolérance de ce traitement est bonne, aucun effet indésirable grave n'est relevé, notamment aucun cas de pneumopathie liée au Lipiocis®. Il n'y a pas de corrélation statistiquement significative entre la survie et l alpha-foetoprotéïne (p=0,14), le score clinique BCLC et l'existence d une thrombose portale (p=0,36). CONCLUSION : Cette étude a mis en évidence un gain de survie satisfaisant et nos résultats sont en accord avec les données de la littérature. Cette approche thérapeutique semble intéressante par son efficacité, sa bonne tolérance et son coût. Il s'agit d'une possibilité simple d utilisation d'une irradiation ciblée qui laissent entrevoir d'autres possibilités thérapeutiques vectorisées qui sont en cours d'évaluation.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Mechanical thrombectomy with the ERIC retrieval device: initial experience

International audienceOBJECTIVE:To report our experience with the Embolus Retriever with Interlinked Cage (ERIC) stentriever for use in mechanical endovascular thrombectomy (MET).METHODS:Thirty-four consecutive patients with acute stroke (21 men and 13 women; median age 66 years) determined appropriate for MET were treated with ERIC and prospectively included over a 6-month period at three different centers. The ERIC device differs from typical stentrievers in that it is designed with a series of interlinked adjustable nitinol cages that allow for fast thrombus capture, integration, and withdrawal. The evaluated endpoints were successful revascularization (Thrombolysis in Cerebral Infarction (TICI) 2b-3) and good clinical outcomes at 3 months (modified Rankin Scale (mRS) 0-2).RESULTS:Locations of the occlusions included the middle cerebral artery (13 patients), terminal carotid artery (11 patients), basilar artery (1 patient), and tandem occlusions (9 patients). IV thrombolysis was performed in 20/34 (58.8%) patients. Median times from symptom onset to recanalization and from puncture to recanalization were 325.5 min (180-557) and 78.5 min (14-183), respectively. Used as the first-line device, ERIC achieved a successful recanalization in 20/24 (83.3%) patients. Successful recanalization was associated with lower National Institutes of Health Stroke Scale scores at 24 h (8±6.5 vs 21.5±2.1; p=0.008) and lower mRS at 3 months (2.7±2.1 vs 5.3±1.1; p=0.04). Three procedural complications and four asymptomatic hemorrhages were recorded. Good clinical outcomes at 3 months were seen in 15/31 (48.4%) patients.CONCLUSIONS:The ERIC device is an innovative stentriever allowing fast, effective, and safe MET

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Background: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. Methods: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Findings: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p<0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons