Different outcome of six homozygotes for prothrombin A20210A gene variant

Prothrombin G20210A gene variant (FII G20210A) is a risk factor for venous thrombotic disease while conflicting results have been reported for the risk of arterial thrombotic events. However, vascular episodes were absent in up to 40% of the 67 homozygotes for the G20210A described so far, which indicates that the clinical expression depends on additional risk/trigger factors. We describe six homozygotes for the G20210A variant, among which the first pair of siblings (cases n. 3 and 4) reported so far that displayed a strongly heterogeneous clinical outcome. Case 1, a female of 27 years, developed a full thrombosis of common femoral, superficial and popliteal veins. She assumed oral contraceptives in the last two years. Case n. 2, 34 years old, suffered of recurrent pregnancy loss in absence of any causative alteration. Cases n. 3 and n. 5 experienced arterial thrombotic disease, i.e., juvenile myocardial infarction (40 years old) and stroke (48 years old), respectively, in absence of other risk factors. Finally, cases n. 4 and 6 identified as homozygotes for the FII G20210A variant being consanguineous of symptomatic subjects bearing the variant, did not experience any episode of venous nor arterial disease. Both of them have chronic liver disease with an impairement of the prothrombin time INR. Thus, homozygotes for the G20210A are at risk for arterial (in addition to venous) thromobotic events; chronic liver disease might modulate this risk

The Clinical Variability of Maternally Inherited Diabetes and Deafness Is Associated with the Degree of Heteroplasmy in Blood Leukocytes

Context: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue. Objective: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes. Participants: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded. Results: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA1c was also found and remained significant after adjustment for age at molecular sampling and gender. Conclusions: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD. Heteroplasmy levels are at least one of the determinants of the severity of the phenotype of maternally inherited diabetes and deafness

Airway and Esophageal Stenting in Patients with Advanced Esophageal Cancer and Pulmonary Involvement

BACKGROUND: Most inoperable patients with esophageal-advanced cancer (EGC) have a poor prognosis. Esophageal stenting, as part of a palliative therapy management has dramatically improved the quality of live of EGC patients. Airway stenting is generally proposed in case of esophageal stent complication, with a high failure rate. The study was conducted to assess the efficacy and safety of scheduled and non-scheduled airway stenting in case of indicated esophageal stenting for EGC. METHODS AND FINDINGS: The study is an observational study conducted in pulmonary and gastroenterology endoscopy units. Consecutive patients with EGC were referred to endoscopy units. We analyzed the outcome of airway stenting in patients with esophageal stent indication admitted in emergency or with a scheduled intervention. Forty-four patients (58+/-\-8 years of age) with esophageal stenting indication were investigated. Seven patients (group 1) were admitted in emergency due to esophageal stent complication in the airway (4 fistulas, 3 cases with malignant infiltration and compression). Airway stenting failed for 5 patients. Thirty-seven remaining patients had a scheduled stenting procedure (group 2): stent was inserted for 13 patients with tracheal or bronchial malignant infiltration, 12 patients with fistulas, and 12 patients with airway extrinsic compression (preventive indication). Stenting the airway was well tolerated. Life-threatening complications were related to group 1. Overall mean survival was 26+/-10 weeks and was significantly shorter in group 1 (6+/-7.6 weeks) than in group 2 (28+/-11 weeks), p<0.001). Scheduled double stenting significantly improved symptoms (95% at day 7) with a low complication rate (13%), and achieved a specific cancer treatment (84%) in most cases. CONCLUSION: Stenting the airway should always be considered in case of esophageal stent indication. A multidisciplinary approach with initial airway evaluation improved prognosis and decreased airways complications related to esophageal stent. Emergency procedures were rarely efficient in our experience

Fully versus partially covered self-expandable metal stents in benign esophageal strictures

International audienc

Advanced glycation end products can induce glial reaction and neuronal degeneration in retinal explants

Background/aims: Neuronal degeneration has been reported to occur in diabetic retinopathy before the onset of detectable microvascular abnormalities. To investigate whether advanced glycation end products (AGE) could be directly responsible for retinal neurodegeneration, retinal explants were incubated with glycated bovine serum albumin (BSA). Methods: Retinal explants obtained from non-diabetic adult rats were incubated 4 days with or without 200 μg/ml glycated BSA. Neural apoptosis was quantified by terminal dUTP nick end labelling (TUNEL) binding and immunostaining with anti-cleaved caspase-3 antibody. Expression of glial fibrillary acidic protein (GFAP) was localised by immunofluorescence. Results: TUNEL and cleaved caspase-3 positive cells increased significantly by 2.2-fold and 2.5-fold in retinal explants incubated in glycated BSA (p<0.05), respectively. The ganglion cell layer was the most sensitive retinal layer to the glycated BSA. Neuronal degeneration was confirmed by the increased GFAP labelling in Müller glial cells from retinal explants treated with glycated BSA. Conclusion: These results suggest that AGE could induce retinal neurodegeneration in the absence of blood perfusion. Cells in the ganglion cell layer appeared to be the most sensitive as in diabetic retinopathy and its animal models. AGE toxicity could therefore contribute to the early pathological mechanisms of diabetic retinopathy

ECLIPSE 2017: NEW RESULTS ON THE DYNAMICAL INNER-CORONA

The total solar eclipse of 21 Aug. 2017 was observed by our teams in excellent conditions for almost 1 hour (from Oregon at 17h12, Idaho 17h27, see Fig. 1, Wyoming 17h36 and Missouri, 18h12 U.T.). Excellent images were recorded in white-light (W-L), including a very high spatial-temporal resolution (HR) sequence covering faint dynamical phenomena related to an exceptionally slow CME that evolved over the E-limb. In addition: i) The overall polarized K-corona, from linearly polarized images taken in 12 positions with a green filter, was analyzed, to be compared to the latest quantitative magnetic dynamical coronal modeling of the Mikic team (Mikić et al. 2018). The complex fine scale structure reflecting the magnetic field topology is analyzed using specially designed algorithms with suggestion of a more turbulent field in the outer corona above r= 2Rs. ii) The more simple Polar-cap Regions are considered to compare the impressive fine-scale more linear W-L plumes with the EUV plumes simultaneously observed in the lower corona with the AIA filtergrams of the SDO mission; we integrate 60 successive AIA images taken with the 171, 193, 211 Å filters to improve the S/N ratio of EUV frames. The new view of dynamical polar plumes is illustrated at different temperature regimes, including a high temperature regime. Some evidence of fast propagating transverse waves is obtained by comparing deep spatially Fourier-filtered W-L images of plumes and jets separated by typically 1 min of time; amplitudes are larger for larger radial distances, suggesting that they reflect the propagation of alfvenic disturbances and possibly their dissipation. iii) The most notable dynamic phenomenon is analyzed at the E-limb: it is a slow CME that shows a constant 250 km/s velocity from the LASCO (SoHO) observations. It is analyzed here in W-L with HR eclipse images and with images from the SECCHI EUV filtergrams of the STEREO mission and from the AIA of the SDO mission. Very small scale and faint moving and curved W-L features at r= 1.7 Rs, possibly owning to high disrupted loops, are analyzed for the 1st time with a 20 sec temporal resolution movie; falling back remnants of the erupted high latitude polar crown filament-prominence found at the feet of the CME are detected in W-L, well after the eruption. It is suggested that such processes are a component of the slow wind that is more easily demonstrated at time of this minimum corona using eclipse images in the r = 1.5 to 2 Rs region where instabilities grow and outwardly propagate.(Boulade et al. (1997) Tavabi et al. (2018