Renal Disease in Patients with Type 2 Diabetes: Magnitude of the Problem, Risk Factors and Preventive Strategies.
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Mesocircuit mechanisms in the diagnosis and treatment of disorders of consciousness.
The 'mesocircuit hypothesis' proposes mechanisms underlying the recovery of consciousness following severe brain injuries. The model builds up from a single premise that multifocal brain injuries resulting in coma and subsequent disorders of consciousness produce widespread neuronal death and dysfunction. Considering the general properties of cortical, thalamic, and striatal neurons, a lawful and specific circuit-level mechanism is constructed based on these known anatomical and physiological specializations of neuronal subtypes. ⋯ Many studies have examined predictions of the mesocircuit model; here we first present the model and review the accumulated evidence for several predictions of model across multiple stages of recovery function in human subjects. Recent studies linking the mesocircuit model, the ABCD model, and interactions with the frontoparietal network are reviewed. Finally, theoretical implications of the mesocircuit model at the neuronal level are considered to interpret recent studies of deep brain stimulation in the central lateral thalamus in patients recovering from coma and in new experimental models in the context of emerging understanding of neuronal and local circuit mechanisms underlying conscious brain states.
Immunosuppressive agents have enabled the development of allogenic transplantation during the last 40 years, allowing considerable improvement in graft survival. However, several issues remain such as the nephrotoxicity of calcineurin inhibitors, the cornerstone of immunosuppressive regimens and/or the higher risk of opportunistic infections and cancers. Most immunosuppressive agents target T cell activation and may not be efficient enough to prevent allo-immunization in the long term. ⋯ Agents targeting this costimulation pathways are currently evaluated in clinical trials. Immunosuppressive agents for ABMR treatment are scarce since anti-CD20 agent rituximab and proteasome inhibitor bortezomib have failed to demonstrate an interest in ABMR. New drugs focusing on antibodies removal (imlifidase), B cell and plasmablasts (anti-IL-6/IL-6R, anti-CD38…) and complement inhibition are in the pipeline, with the challenge of their evaluation in such a heterogeneous pathology.
From islet of Langerhans transplantation to the bioartificial pancreas.
Type 1 diabetes is a disease resulting from autoimmune destruction of the insulin-producing beta cells in the pancreas. When type 1 diabetes develops into severe secondary complications, in particular end-stage nephropathy, or life-threatening severe hypoglycemia, the best therapeutic approach is pancreas transplantation, or more recently transplantation of the pancreatic islets of Langerhans. Islet transplantation is a cell therapy procedure, that is minimally invasive and has a low morbidity, but does not display the same rate of functional success as the more invasive pancreas transplantation because of suboptimal engraftment and survival. ⋯ A successful bioartificial pancreas would address the issues of engraftment, survival and rejection. Inclusion of unlimited sources of insulin-producing cells, such as xenogeneic porcine islets or stem cell-derived beta cells would further solve the problem of organ shortage. This article reviews the current status of clinical islet transplantation, the strategies aiming at developing a bioartificial pancreas, the clinical trials conducted in the field and the perspectives for further progress.
Unraveling complexity of antibody-mediated rejections, the mandatory way towards an accurate diagnosis and a personalized treatment.
Antibody-mediated rejection (ABMR) remains one of the most challenging issues after organ transplantation and particularly after kidney transplantation. Despite many progresses during the last decade, ABMR is still the main cause of kidney graft loss and this all over the post- transplant period. In this review, we describe the recent knowledge about molecular and cellular mechanisms involved in ABMR. ⋯ ABMR diagnosis relies on the presence of renal injuries and donor-specific antibodies (DSA) (HLA and non HLA antibodies) with sometimes the evidence of interaction between DSA and graft endothelium. Regularly revised during expert conferences, ABMR definition is currently categorized as active or chronic active.  The emergence of validated molecular assays targeting a better phenotyping of ABMR and the recent advances regarding the detrimental effect of DSA directed against minor antigens open the way to a better assessment of the heterogeneity of ABMR. In this review, we will address new aspects of ABMR regarding its mechanisms, diagnosis and treatments.