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The fibrotic stroma characterizing pancreatic ductal adenocarcinoma (PDAC) derives from a progressive tissue rigidification, which induces epithelial mesenchymal transition and metastatic dissemination. The aim of this study was to investigate the influence of matrix stiffness on PDAC progression by analyzing the proteome of PDAC-derived extracellular vesicles (EVs). PDAC cell lines (mPDAC and KPC) were grown on synthetic supports with a stiffness close to non-tumor (NT) or tumor tissue (T), and the protein expression levels in cell-derived EVs were analyzed by a quantitative MS^E label-free mass spectrometry approach. Our analysis figured out 15 differentially expressed proteins (DEPs) in mPDAC-EVs and 20 DEPs in KPC-EVs in response to matrix rigidification. Up-regulated proteins participate to the processes of metabolism, matrix remodeling, and immune response, altogether hallmarks of PDAC progression. A multimodal network analysis revealed that the majority of DEPs are strongly related to pancreatic cancer. Interestingly, among DEPs, 11 related genes (ACTB/ANXA7/C3/IGSF8/LAMC1/LGALS3/PCD6IP/SFN/TPM3/VARS/YWHAZ) for mPDAC-EVs and 9 (ACTB/ALDH2/GAPDH/HNRNPA2B/ITGA2/NEXN/PKM/RPN1/S100A6) for KPC-EVs were significantly overexpressed in tumor tissues according to gene expression profiling interaction analysis (GEPIA). Concerning the potential clinical relevance of these data, the cluster of ACTB, ITGA2, GAPDH and PKM genes displayed an adverse effect (p < 0.05) on the overall survival of PDAC patients.

Several countries have recently reassessed the international risk of variant Creutzfeldt-Jakob disease (vCJD) transmission through transfusion of blood and blood components (red blood cells, platelets and plasma) and relaxed donor deferrals based on geographic and transfusion exposure in countries formerly considered to be high risk, such as the UK. In this regard, the European Blood Alliance organised a consensus meeting of experts and involved professionals to discuss current knowledge, epidemiological data, prevention and various methods for assessing the risk of transfusion-transmitted vCJD, as well as to develop an appropriate position on possible approaches to address these challenges in Europe. Participants reached a consensus that the current risk of transfusion-transmitted vCJD associated with blood donors who either travelled to or received transfusions in the UK during the vCJD outbreak is minimal. In addressing such risks, it would be pragmatic that assessments and guidelines are developed by European expert bodies, rather than individual assessments by Member States. Regardless of the approach used, European or national, a qualitative risk assessment based on a review and analysis of available data, considering all the uncertainties and experiences of other countries, would provide crucial information to reassess blood donation strategies regarding the transfusion-associated vCJD risk.

Rituximab (RTX), an anti CD20 monoclonal antibody, is now a gold standard treatment for several auto-immune and chronic inflammatory diseases. Receiving RTX exposes patients to more severe infections as vaccinations become virtually inefficient in terms of B cell responses. During the COVID-19 crisis, RTX-exposed patients exhibited more severe forms of the disease, and in some cases, the introduction of RTX was delayed or avoided to protect patients as much as possible against SARS-CoV-2 infections. We retrospectively collected cellular and humoral responses from thirteen patients with dermatological and rheumatological autoimmune diseases who had been vaccinated after receiving RTX. Memory T cells subsets from patients that exposed to RTX showed few differences when compared to a cohort of healthy donors. The IFNᵧ ELISpot assay using SARS-CoV-Prot_S1 showed that eight patients exhibited a positive response that was neither correlated to the time between RTX infusion and the sampling nor to the time between RTX and the vaccination. Conversely, analysis of the SARS-CoV-2 serology showed a clearly lower binding antibody units per mL in case of recent RTX infusion. The safe threshold forconsistently positive serology was to vaccinate at least 300 days after RTX infusion (p = 0.02). Our data illustrate the difficulty in obtaining a satisfactory response to vaccination after RTX treatment within almost a year after the latest infusion, and emphasize the need to better evaluate the risk of relapses in auto-immune diseases before administering RTX in order to maintain RTX only in patients whose medical situation requires it.