Vue d'ensemble des pratiques médicales dans la DMLA exsudative en France

Wet AMD is characterized by the formation of choroidal neovascularization, mediated by vascular endothelial growth factor (VEGF) and responsible for a decrease in visual acuity and metamorphopsia of sudden onset. Intravitreal anti-VEGF can stabilize or even improve visual acuity. Although there is a consensus among ophthalmologists about the induction phase injection of anti-VEGF, there appear to be differences in practice regarding therapeutic treatment modalities. The goal of this work was to explore this hypothesis and to better understand real life practices

The dual Syk/JAK inhibitor cerdulatinib antagonizes B-cell receptor and microenvironmental signaling in chronic lymphocytic leukemia

Purpose: B-cell receptor (BCR)-associated kinase inhibitors such as ibrutinib have revolutionised the treatment of chronic lymphocytic leukemia (CLL). However, these agents are not curative and resistance is already emerging in a proportion of patients. Interleukin-4 (IL-4), expressed in CLL lymph nodes, can augment BCR-signalling and reduce the effectiveness of BCR-kinase inhibitors. Therefore simultaneous targeting of the IL-4- and BCR-signalling pathways by cerdulatinib, a novel dual Syk/JAK inhibitor currently in clinical trials (NCT01994382), may improve treatment responses in patients. Experimental Design: PBMCs from CLL patients were treated with cerdulatinib alone or in combination with venetoclax. Cell death, chemokine and cell signalling assay were performed and analysed by flow cytometry, immunoblotting, Q-PCR and ELISA as indicated. Results: at concentrations achievable in patients, cerdulatinib inhibited BCR- and IL-4-induced downstream signalling in CLL cells using multiple read outs and prevented anti-IgM- and nurse-like cell (NLC)-mediated CCL3/CCL4 production. Cerdulatinib induced apoptosis of CLL cells, in a time- and concentration dependent manner, and particularly in IGHV unmutated samples with greater BCR-signalling capacity and response to IL-4, or samples expressing higher levels of sIgM, CD49d+ or ZAP70+. Cerdulatinib overcame anti-IgM, IL-4/CD40L or NLC-mediated protection by preventing upregulation of MCL-1- and BCL-XL, however BCL-2 expression was unaffected. Furthermore in samples treated with IL-4/CD40L, cerdulatinib synergised with venetoclax in vitro to induce greater apoptosis than either drug alone. Conclusion: cerdulatinib is a promising therapeutic for the treatment of CLL either alone or in combination with venetoclax, with the potential to target critical survival pathways in this currently incurable disease<br/

Using the West Midlands CONCERT to characterise regional incidence of acute-onset post cataract surgery endophthalmitis.

BACKGROUND Whilst research and innovation is embedded within the UK's National Health Service (NHS) constitution, Doctors-in-training have little opportunity to contribute to designing, leading and recruiting into clinical trials or cohort studies. We formed the West Midlands Collaborative Ophthalmology Network for Clinical Effectiveness & Research by Trainees (The West Midlands CONCERT) and undertook a characterisation of post cataract surgery endophthalmitis as a proof-of-concept study to test the feasibility of the CONCERT model. METHODS Doctors-in-training formed a collaborative working group to test the concept of delivering a pan-regional clinical effectiveness study across multiple hospital sites by performing retrospective analyses of post cataract endophthalmitis over a 6-year period. RESULTS Overall, 157,653 cataract surgeries were performed by participating centres accredited to deliver the Royal College of Ophthalmologists training curriculum. Thirty-eight cases of post cataract endophthalmitis were identified, giving an incidence of 2.41 per 10,000 cases (0.0241%). A further 15 endophthalmitis cases presented who had surgery in non-training centres, giving a total of 53 cases. The most common organisms were S. epidermidis (14 (51.9%)) and P. aeruginosa (5 (18.5%)). Anterior-chamber and vitreous sampling yielded positive culture in 33.3% (6/18) and 50.9% (27/53), respectively. At 6 months follow-up, 19 (51.4%) patients achieved visual acuities of ≤0.5 LogMAR. Repeat intravitreal injections (11 (20.8%)) and vitrectomy (n = 22 (41.5%)) were not associated with better outcomes. CONCLUSIONS Using post cataract endophthalmitis as a pilot cohort, this study highlights the feasibility of using the CONCERT model for studies across multiple sites. A UK-CONCERT could provide a powerful infrastructure enabling characterisation of patient cohorts and a platform for high-quality interventional studies, improving patient care