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Type 1 diabetes (T1D) is a chronic metabolic disease of unknown etiology that results from β-cell destruction. The onset of the disease, which arises after a long asymptomatic period of autoimmune attack, may be followed by a relapsing and remitting progression, a phenomenon that is most evident during the partial remission phase (PR). This stage lasts for a few months, shows minor requirements of exogenous insulin and could be explained by a recovery of immunological tolerance. This study aims to identify new biomarkers at early stages of pediatric T1D that reflect immunoregulatory changes. To that end, pediatric patients with T1D (n = 52) and age-related control subjects (n = 30) were recruited. Immune response-related molecules and lymphocyte subsets were determined starting at T1D onset and until the second year of progression. Results showed that circulating TGF-β levels decreased during PR, and that betatrophin concentration was increased in all the considered stages without differing among studied checkpoints. Moreover, an increase of regulatory T, B and NK subsets was found during T1D progression, probably reflecting an attempt to restore self-tolerance. By contrast, a reduction in monocyte levels was observed at the early stages of diabetes. The results reveal significant changes in immunological parameters during the different early stages of T1D in children, which could ultimately serve as potential biomarkers to characterize the progression of T1D. [ABSTRACT FROM AUTHOR]

Background: The epidermal growth factor receptor (EGFR) is a member of the ErbB family of membrane tyrosine-kinase receptors. Studies exploring the prognostic role of EGFR-overexpression in early breast cancer have shown variable results, and the true prognostic value of EGFR is unknown.Methods: A systematic review of identified publications exploring the association between EGFR-overexpression (as defined from different techniques and cut-offs) and outcomes [disease-free (DFS) and, overall survival (OS)] in women with early breast cancer. The hazard ratios (HR) for DFS and OS were weighted and pooled in a meta-analysis using generic inverse variance and random effects modeling.Results: Fifty-three studies comprising 21,418 women were included. EGFR-overexpression was found in 27% of the patients. Primary analysis included studies reporting HRs from multivariable analyses (10 studies including 4857 patients with HRs for OS and 17 studies comprising 8747 patients with HRs for DFS), EGFR-overexpression was associated with worse OS (HR 1.98, 95% CI: 1.59-2.47, p < .001) and DFS (HR 1.59, 95% CI 1.30-1.95, p < .001). The influence of EGFR overexpression on DFS was greater in women with triple negative tumors compared to women with non-triple negative tumors (HR 2.35 versus HR 1.45, respectively; p = .01). Analysis looking at odd ratios for both 5-year and 10-year for DFS and OS showed similar results.Conclusion: EGFR-overexpression appears to be associated with reduced OS and DFS in women with early breast cancer. Patients with triple negative and EGFR-overexpression have poorer OS and DFS than those with triple negative tumors and normal EGFR expression. [ABSTRACT FROM AUTHOR]

Autoimmune diseases (AIDs) are caused by the loss of self-tolerance and destruction of tissues by the host's immune system. Several antigen-specific immunotherapies, focused on arresting the autoimmune attack, have been tested in clinical trials with discouraging results. Therefore, there is a need for innovative strategies to restore self-tolerance safely and definitively in AIDs. We previously demonstrated the therapeutic efficacy of phosphatidylserine (PS)-liposomes encapsulating autoantigens in experimental type 1 diabetes and multiple sclerosis. Here, we show that PS-liposomes can be adapted to other autoimmune diseases by simply replacing the encapsulated autoantigen. After administration, they are distributed to target organs, captured by phagocytes and interact with several immune cells, thus exerting a tolerogenic and immunoregulatory effect. Specific PS-liposomes demonstrate great preventive and therapeutic efficacy in rheumatoid arthritis and myasthenia gravis. Thus, this work highlights the therapeutic potential of a platform for several autoimmunity settings, which is specific, safe, and with long-term effects. Upon administration, apoptotic-mimicking phosphatidylserine (PS)-liposomes encapsulating disease-specific autoantigens are distributed to target organs and captured by antigen-presenting cells, such as dendritic cells, macrophages and B cells, which mount a tolerogenic response involving classical and non-classical regulatory T cells, regulatory B cells, anergic and exhausted T lymphocytes, which in turn arrest the development of autoimmune diseases like type 1 diabetes, multiple sclerosis, rheumatoid arthritis and myasthenia gravis. Created with BioRender.com. [Display omitted] • PS-liposomes encapsulating autoantigens promote specific self-tolerance. • Intravenous injection achieves quick and efficient biodistribution to target organs. • Antigen-presenting cells capture PS-liposomes and induce a tolerogenic response. • PS-liposomes arrest the development of rheumatoid arthritis and myasthenia gravis. • These synthetic vesicles are a solid candidate strategy in the clinical setting. [ABSTRACT FROM AUTHOR]

Abstract: In the past 10 years, sentinel lymph node biopsy (SLNB) has become a safe and accurate method for axillary staging. Several recent publications worldwide have been progressively elucidating old controversies. The list of clinical scenarios in which SLNB was initially contraindicated seems to be dwindling as experience with this technique increases. Here we discuss the suitability of SLNB in the settings of microinvasive cancer, after breast or axillary surgery and after neoadjuvant chemotherapy. [Copyright &y& Elsevier]