Intravitreal ranibizumab for age-related macular degeneration : optical coherence tomography guided retreatment intervals and their intra- and inter-individual variability

Purpose: To determine whether the need for retreatment after an initial phase of 3 monthly intravitreal injections of ranibizumab shows an intra-individual regular rhythm and to what degree it varies between different patients. Methods: Prospective study with 42 patients with exudative AMD, treatment naïve. Loading dose of 3 monthly doses of ranibizumab (0,5 mg), followed by a 12 months pro re nata (PRN) regimen according to early exudative signs on HD-OCT Cirrus, Zeiss. The follow-up visits were intensified (week 4, 5, 6, 7, 8, 10, 12, 14, 16, 20, etc after each injection) in order to detect recurrences early, and injection followed within 3 days in cases of subretinal fluid, cysts, or central thickness increase of>50microns. Intervals were calculated between injections for the 12 month follow-up with PRN treatment. Variability was expressed as standard deviation (SD). Results: Visual acuity (VA) improved from a mean ETDRS score of 61.6 (SD 10.8) at baseline to 68.0 (SD 10.2) at month 3 and to 74.7(SD 9.0) at month 12. The 15 patients who have already completed the study showed maintenance of the VA improvement. Central foveal thickness improved from a mean value of 366 microns (baseline) to 253 microns (month 3), well maintained thereafter. Mean number of injections was 8.8 (SD 3.5,range 0-12) per 12 months of follow-up (after 3 doses), with mean individual treatment-recurrence (TR) intervals ranging from 28->365 days (mean 58). Intraindividual variability of TR intervals (SD) was 7.1 days as a mean value (range 1.7¡V22.6). It ranged within 20% of the mean intra-individual interval for 30 (91%) and within 15% for 21 patients (64%). The first interval was within 1 week of the mean intra-individual interval in 64% and within 2 weeks in 89% of patients. Conclusions: The majority of AMD patients showed a relatively stable rhythm for PRN injections of ranibizumab after initial loading phase, associated with excellent functional/anatomical results. The initial interval last loading dose-first recurrence may have a predictive value for further need of treatment, potentially facilitating follow-up and patient care.

Comment on "Geochemistry, petrogenesis and tectonic setting of the Samothraki mafic suite, NE Greece: Trace-element, isotopic and zircon age constraints'' by N. Koglin, D. Kostopoulos & T. Reischmann [Tectonophysics 473, 53-68 (doi:10.1016/j.tecto.2008.10.028)]

The work by Koglin et al. (Koglin, N., Kostopoulos, D., Reichmann, T., 2009. Geochemistry, petrogenesis and tectonic setting of the Samothraki mafic Suite, NE Greece: Trace-element, isotopic and zircon age constraints. Tectonophysics 473, 53-68. doi: 10.1016/j.tecto.2008.10.028), where the authors have proposed to nullify the scenario presented by Bonev and Stampfli (Bonev, N., Stampfli, G., 2008. Petrology, geochemistry and geodynamic implications of Jurassic island arc magmatism as revealed by mafic volcanic rocks in the Mesozoic low-grade sequence, eastern Rhodope, Bulgaria. Lithos 100, 210-233) is here Put under discussion. The arguments for this proposal are reviewed in the light of available stratigraphic and radiometric age constraints, geochemical signature and tectonics of highly relevant Jurassic ophiolitic suites occurring immediately north of the Samothraki mafic suite. Our conclusion is that the weak arguments and the lack of knowledge on the relevant constraints from the regional geologic information make inconsistent the Proposal and the model of these authors. (C) 2009 Elsevier B.V. All rights reserved.

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

Socialisme et mouvements ouvriers français et italien en guerre : Que faire lorsque le conflit éclate ?

« Reconnaissons-le comme un fait, soulignait François Hollande lors du lancement des commémorations du centenaire en novembre 2013, lorsque la mobilisation générale fut proclamée, il n'y eut plus qu'un seul pays, une seule Nation, une seule armée ». A l'heure où les commémorations officielles du premier conflit mondial battent leur plein, il est plus que jamais impossible de s'abstraire du rapport dialectique qui s'instaure entre « usages publics et politiques de l'histoire » et construction de l'histoire savante. Aujourd'hui, le monde ouvrier, les vaincus, semblent ainsi être invoqués pour souligner substantiellement leur « adhésion » substantielle à « leur » nation en guerre. Les mondes et les mouvements ouvriers, dans toute leur complexité sociale et politique s'estompent de la recherche historique comme ont disparu ou presque les questions liées aux rapports de force sociopolitiques. Cette contribution se propose de revenir sur l'un des noeuds historiographiques concernant les socialismes en guerre, soit celui de leur « entrée » dans le conflit. Il s'agit de comprendre comment « la guerre fait irruption » dans les débats du socialisme international, en envisageant les divers positionnements par rapport au "choix" de l'intervention, notamment la question du "revirement" d'une social-démocratie hostile à la guerre qui entre néanmoins en guerre en usant parfois d'une rhétorique patriotique voire nationaliste. Pour ce faire, deux cas d'études ont été choisis partant de deux réalités sociopolitiques différentes qui, chacune à leur manière, offrent une palette des manières qu'a eues la socialdémocratie de se positionner face à la guerre. D'un côté, l'« exception » italienne, de l'autre le « revirement » patriotique français. En point de mire : comprendre si et dans quelle mesure la guerre constitue un tournant, une rupture dans l'histoire des sociétés considérées, et quelles en sont les limites.

Prospective study evaluating the predictability of need for retreatment with intravitreal ranibizumab for age-related macular degeneration.

PURPOSE: To investigate the rhythm and predictability of the need for retreatment with intravitreal injections of ranibizumab for neovascular age-related macular degeneration (nAMD). METHODS: This prospective study enrolled 39 patients with treatment-naïve nAMD. After three loading doses of intravitreal ranibizumab, patients underwent an intensified follow-up for 12 months (initially weekly, then with stepwise increases to every 2 weeks and to monthly after each injection). Patients were retreated on an as-needed basis if any fluid or increased central retinal thickness (CRT) (>50μm) was found on spectral domain optical coherence tomography (OCT). Statistical analysis included patients who received at least two retreatments (five injections). RESULTS: A mean of 7.5 injections (range 0-12) were given between months 3 and 15. The mean visual acuity increased by 13.1 and 12.6 ETDRS letters at months 12 and 15 respectively. Two or more injection-retreatment intervals were found in 31 patients. The variability of their intra-individual intervals up to 14 weeks was small (SD 0-2.13 weeks), revealing a high regularity of the retreatment rhythm. The SD was correlated with the mean interval duration (r = 0.89, p < 0.001). The first interval was a good predictor of the following intervals (regression coefficient =0.81). One retreatment criterion was stable in 97 % of patients (cysts or subretinal fluid). CONCLUSION: The results of this study demonstrate a high intra-individual predictability of retreatment need with ranibizumab injections for nAMD. These findings may be helpful for developing individualized treatment plans for maintained suppression of disease activity with a minimum of injections and visits.

Esotropie précoce: résultats à long terme d'une série de 82 cas opérés par myopexie rétro-équatoriale et recul simultané des deux muscles droits médiaux avant l'âge de 24 mois [Early-onset esotropia operated before the age of 24 months: long-term results of Cüpper's retropexy combined with simultaneous recession of both medial recti]

BACKGROUND: When and how to operate an early-onset esotropia (onset before 6 months of age) is still controversial. We conducted a retrospective study of such patients operated before the age of 24 months. PATIENTS AND METHODS: 82 patients were operated by one surgeon (GK) and followed by the same team. At 5 years post-operation, evaluation criteria included the residual angle of deviation, visual acuity (Birkhäuser Nr 505, 5 m) and binocularity (Lang stereotest I, Bagolini glasses). RESULTS: At 5 years, the residual angle was excellent (0 degrees to + 5 degrees ) in 67 % good, (>+5 degrees to +10 degrees or 0 to -5 degrees ) in 23 %, and poor (>+10 degrees or <-5 degrees ) in 10 %. During the 5 years of follow-up the rate of reoperation was 9.7 %. Isoacuity was obtained in 62 %, slight amblyopia (2 lines of interocular difference) was present in 32 %, and average amblyopia (> 3 lines of interocular difference) was noted in 6 %. Simultaneous perception was present in 53 %, whereas one eye was suppressed or results were undetermined in 47 %. No patient demonstrated stereoscopy using the Lang's stereotest I. CONCLUSION: The results from our study demonstrate that early surgery of early-onset esotropia has a favourable outcome on both visual acuity and the residual angle of strabismus. Simultaneous perception was achieved in 53 %. These figures are comparable to the results of the ELISSS multicentric study.

Prevention of age-associated dementia.

The advancement of medical sciences during the last century has resulted in a considerable increase in life expectancy. As more people live to old age, one of the most fundamental questions of the 21st century is whether the number of individuals suffering from dementia will also continue to increase. Alzheimer's disease (AD) accounts for the majority of cases of dementia in the elderly, but there is currently no curative treatment available. Several strategies have been introduced for treatment, the most recent strategy of which was the immunization of patients using antibodies against Abeta, which is a naturally occurring, even though misfolded peptide in the AD brain. Both active and passive immunization routes have been shown to reduce the pathology associated with Abeta accumulation in brains of genetically designed animal models. However, despite tremendous efforts, no unequivocal proof of therapeutic efficacy could be shown in AD patients. Particularly, the persistence of the neurofibrillary tangles in immunized brains and the issue of inducing cerebral amyloid angiopathy are major limiting factors of antibody therapy. Furthermore, physical activity, a healthy immune system and nutritional habits are suggested to protect against the onset of age-associated dementia. Thus, accumulative evidence suggests that an early integrated strategy, combining pharmacological, immunological, nutritional and life-style factors, is the most pragmatic approach to delay the onset and progression of age-associated dementia.

Facteurs de risque fracturaire, nouveaux traitements: comment evolue la prise en charge de l'ostéoporose de la personne agée [Fracture risk, new treatments: how does the management of the osteoporosis of elderly change?]

Osteoporosis of elderly is a growing medical, economic and health-care problem. It is due to the increase of the life expectancy and the number of osteoporotic fractures. With the new Swiss-specific tool FRAX and the development of inpatients fracture trajectory, we can better identify patients with high risk of fracture. An appropriate treatment can be proposed more quickly. The follow-up of bone markers increases the treatment efficiency. With a better identification, treatment and follow-up of osteoporosis of elderly patients, we can ameliorate the patient's quality of life and decrease the number of osteoporotic fractures with a good cost-effectiveness ratio.