Presse Med
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This manuscript explores the international variability in the diagnosis and management of disorders of consciousness (DoC). The identification, evaluation, intervention, exploration, prognostication and limitation of therapy for patients with DoC is reviewed through an international lens. The myriad factors that impact the diagnosis and management of DoC including 1) financial, 2) legal and regulatory, 3) cultural, 4) religious and 5) psychosocial considerations are discussed. ⋯ It is necessary to promote equity in access to expertise and resources for patients with DoC to enhance the care of patients with DoC worldwide. Improving understanding and management of patients with DoC requires harmonization of existing datasets, development of registries where none exist and establishment of international clinical trial networks that include patients in all phases along the spectrum of care. The work of international organizations like the Curing Coma Campaign can hopefully minimize international variability in the diagnosis and management of DoC and optimize care.
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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.
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The COVID-19 pandemic affects the transplant recipients since March 2020. Transplant centers quickly organized themselves to optimize the management of the immunocompromised patients and to progress in the knowledge of this new disease. To this end, a French Registry was created, which includes all solid organ transplant patients who have developed a SARS Cov2 infection. ⋯ The 60 days-mortality of transplant patients hospitalized for COVID-19 was evaluated at 23% and renal failure plays a major role in the poor prognosis in addition to the classical risk factors described in the general population. The advent of vaccination has been a great relief but transplanted patients have shown a poor vaccine response keeping them at risk of severe disease even after an adapted vaccination scheme. Specific strategies was proposed in this particularly fragile population like increasing vaccine doses or using anti SARS Cov-2 monoclonal antibodies.
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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.