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Traumatic brain injury (TBI) can cause major disability and increases the risk of neurodegeneration. Post-TBI, there is infiltration of peripheral myeloid and lymphoid cells; there is limited information on the peripheral immune response post-TBI in the immature brain—where injury may interfere with neurodevelopment. We carried out two injury types in juvenile mice: invasive TBI with a controlled cortical impact (CCI) and repetitive mild TBI (rmTBI) using weight drop injury and analysed the response at 5- and 35-days post-injury. In the two models, we detected the brain infiltration of immune cells (e.g., neutrophils, monocytes, dendritic cells, CD4+ T cells, and NK cells). There were increases in macrophages, neutrophils, and dendritic cells in the spleen, increases in dendritic cells in blood, and increases in CD8+ T cells and B cells in lymph nodes. These results indicate a complex peripheral immune response post-TBI in the immature brain, with differences between an invasive injury and a repetitive mild injury. [ABSTRACT FROM AUTHOR]

Keywords: retrospective chart review; haemophilia A; immune tolerance induction; inhibitor; recombinant factor VIII Fc fusion protein; rescue therapy EN retrospective chart review haemophilia A immune tolerance induction inhibitor recombinant factor VIII Fc fusion protein rescue therapy 19 25 7 02/04/21 20210101 NES 210101 Dear Editor, Prophylactic factor VIII (FVIII) replacement is the current standard of care for severe haemophilia A but approximately 25%-40% of patients develop inhibitors against exogenous FVIII, rendering FVIII replacement therapy ineffective.1 Eradication of high-titre inhibitors involves immune tolerance induction (ITI): repeated, long-term administration of high-dose FVIII.1 Recombinant FVIII Fc fusion protein (rFVIIIFc [ELOCTATE SP ® sp , Sanofi, Waltham, MA]) is the first extended half-life FVIII approved for haemophilia A.2 Case reports and an initial retrospective chart review suggest that rFVIIIFc ITI may lead to faster tolerization than ITI with standard FVIII concentrates.3,4 This letter reports final clinical outcomes of 29 patients (19 included in the initial analysis) with severe haemophilia A undergoing ITI with rFVIIIFc in a real-world setting.4 We performed a retrospective review of patient charts at 13 sites across the United States and Canada, using previously published methods.4 Briefly, de-identified clinical data were collected from patients with severe haemophilia A and historical high-titre inhibitors, who began first-time or rescue ITI with rFVIIIFc between July 2014 and February 2018 and had >=3 months of exposure to rFVIIIFc ITI. Tolerization was defined as a negative Bethesda titre (<0.6 BU/mL), normal FVIII recovery (>=66% of expected) and rFVIIIFc half-life >=6 hours.5 Altogether, 29 rFVIIIFc ITI patients were identified: 10 first-time (Table 1) and 19 rescue patients (Table 2). [Extracted from the article]