Epsteinhedegaard5847

Due to the high coverage of international vaccination programs, most people worldwide have been vaccinated against common pathogens, leading to acquired pathogen-specific immunity with a robust memory T cell repertoire. While CD8+ anti-tumor cytotoxic T lymphocytes (CTL) are the preferred effectors of cancer immunotherapy, CD4+ T cell help is also required for an optimal anti-tumor immune response to occur. Hence, we investigated whether the pathogen-related CD4+ T cell memory populations could be re-engaged to support the CTLs, converting a weak primary anti-tumor immune response into a stronger secondary one. To this end, we used our PeptiCRAd technology that consists of an oncolytic adenovirus coated with MHC-I-restricted tumor-specific peptides, and developed it further by introducing pathogen-specific MHC-II-restricted peptides. Mice pre-immunized with tetanus vaccine were challenged with B16.OVA tumors and treated with the newly developed hybrid TT-OVA-PeptiCRAd containing both tetanus toxoid- and tumor-specific peptides. selleck chemicals llc Treatment with the hybrid PeptiCRAd significantly enhanced anti-tumor efficacy and induced TT-specific, CD40 ligand-expressing CD4+ T helper cells and maturation of antigen presenting cells (APCs). Importantly, this approach could be extended to naturally occurring tumor peptides (both tumor-associated antigens and neoantigens), as well as to other pathogens beyond tetanus, highlighting the usefulness of this technique to take full advantage of CD4+ memory T cell repertoires when designing immunotherapeutic treatment regimens. Finally, the anti-tumor effect was even more prominent when combined with the immune checkpoint inhibitor anti-PD1, strengthening the rationale behind combination therapy with oncolytic viruses. Copyright ©2020, American Association for Cancer Research.BACKGROUND A consensus on an optical coherence tomography definition of lamellar macular hole (LMH) and similar conditions is needed. METHODS The panel reviewed relevant peer-reviewed literature to reach an accord on LMH definition and to differentiate LMH from other similar conditions. RESULTS The panel reached a consensus on the definition of three clinical entities LMH, epiretinal membrane (ERM) foveoschisis and macular pseudohole (MPH). LMH definition is based on three mandatory criteria and three optional anatomical features. The three mandatory criteria are the presence of irregular foveal contour, the presence of a foveal cavity with undermined edges and the apparent loss of foveal tissue. Optional anatomical features include the presence of epiretinal proliferation, the presence of a central foveal bump and the disruption of the ellipsoid zone. ERM foveoschisis definition is based on two mandatory criteria the presence of ERM and the presence of schisis at the level of Henle's fibre layer. Three optional anatomical features can also be present the presence of microcystoid spaces in the inner nuclear layer (INL), an increase of retinal thickness and the presence of retinal wrinkling. MPH definition is based on three mandatory criteria and two optional anatomical features. Mandatory criteria include the presence of a foveal sparing ERM, the presence of a steepened foveal profile and an increased central retinal thickness. Optional anatomical features are the presence of microcystoid spaces in the INL and a normal retinal thickness. CONCLUSIONS The use of the proposed definitions may provide uniform language for clinicians and future research. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND/AIMS Quantitative analysis of optical coherence tomography angiography (OCT-A) images requires a reproducible approach that accounts for sectoral loss. The objective of this study was to determine whether an index that accounts for both global (perfusion density, PD) and asymmetric loss of perfusion, rather than PD alone, more reliably measures loss of perfusion in patients with glaucoma. METHODS We analysed macular OCT-A scans of 95 glaucoma patients and 59 control subjects. Two-dimensional projection images corresponding to the superficial vascular plexus were exported and analyses performed to calculate global PD and image asymmetry. An unsigned perfusion asymmetry index (PAI) that included PD and asymmetry (with 11 wt) was calculated. Perfusion density and PAI were compared with 10-2 visual field mean deviation and ganglion cell layer (GCL) thickness. RESULTS Median (IQR) visual field mean deviation was -1.73 (-3.76, 0.30) dB for the glaucoma group and 0.67 (0.16, 1.18) dB for the control group. The strength of the correlation with mean deviation was stronger for PAI (r=0.47), compared with PD (r=0.35), whereas with GCL thickness they were comparable (r=0.45 and 0.43, respectively). Compared with controls, mean PD was 12% lower in patients with glaucoma (0.27 vs 0.30), while PAI was 17% lower (0.40 vs 0.48). However, diagnostic accuracy of either PD or PAI was worse than GCL thickness. CONCLUSIONS While PAI yielded better correlation with mean deviation and GCL thickness, and a slightly improved separation between patients with glaucoma and healthy controls, diagnostic accuracy was inferior compared with GCL thickness. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.PURPOSE To evaluate use of infrared meibography video to visualise meibomian gland probing and correlate probe findings of intraductal space with meibography images. METHODS Videos were reviewed and probe findings recorded of 996 probed gland orifices from 38 lower lids. RESULTS 996/997 (99.9%) of gland orifices were successfully probed with 91.8% revealing probe location. There were no false passages. 14% (140/997) of all gland orifices showed whole gland atrophy (WGA) with 99.3% (139/140) probed to 1 mm. Cumulative probe findings for all WGA (not differ significantly from non-WGA) showed 106 (76%), 21 (15%) and 12 (9%) glands with fixed, non-fixed and no resistance (NR), respectively. Lids without WGA showed increased NR/total glands probed while lids with WGAs (≥5) showed increased NR/WGA compared with lids with only 1-4 WGAs (p=0.011, p=0.005, respectively, Mann-Whitney U test) suggesting bimodal NR profile. Visualisation of microtube placement was successfully obtained for therapeutic injections and retrieval of meibum specimens.