Patients with neuropsychological disorders short after stroke have worse functional outcome: a systematic review and meta-analysis.

PURPOSE: To investigate if patients with neuropsychological disorders (neglect, aphasia, or cognitive dysfunction measured with the Mini-mental state examination) short after stroke have different functional outcome at follow-up compared to patients without these disorders. METHODS: Embase, Medline-Ovid, PsycINFO, Cochrane CENTRAL, Web of Science and Google Scholar were systematically searched for cohort studies up to 3 March 2019. PRISMA guidelines were followed. Functional outcome had to be measured with the Barthel Index or the Functional Independence Measure. If at least three studies studying the same neuropsychological disorder reported functional outcome at comparable follow-up, meta-analysis were performed and the quality of evidence was assessed using GRADE. RESULTS: The search resulted in 5398 unique articles and finally 27 articles were included. Pooled results show a standardized mean difference of -0.93 (95% confidence interval [-1.27 to -0.59]), indicating that the group with neglect short after stroke has significant lower functional outcome at follow-up. Regarding aphasia, the standardized mean difference was -0.50 (95% confidence interval [-0.72 to -0.28]). It appears in the limited articles available that patients with cognitive dysfunction have lower scores for functional outcome. CONCLUSIONS: Patients with neglect or aphasia, especially aphasia with comprehension deficits, short after stroke have significant worse functional outcome.Implications for rehabilitationClinicians should perform an extensive screening for neglect, aphasia, and cognitive disorders to make sure to diagnose the different neuropsychological disorders correctly.When patients with neuropsychological disorders are referred for rehabilitation, it can be expected that they need a longer rehabilitation period or may never reach the same level of functioning.Clinicians should pay attention to instructions of training moments outside therapy and involve caregivers and patients family making these training moments more effective.

Activation of CD8⁺ T Cell Responses after Melanoma Antigen Targeting to CD169⁺ Antigen Presenting Cells in Mice and Humans.

The lack of tumor-reactive T cells is one reason why immune checkpoint inhibitor therapies still fail in a significant proportion of melanoma patients. A vaccination that induces melanoma-specific T cells could potentially enhance the efficacy of immune checkpoint inhibitors. Here, we describe a vaccination strategy in which melanoma antigens are targeted to mouse and human CD169 and thereby induce strong melanoma antigen-specific T cell responses. CD169 is a sialic acid receptor expressed on a subset of mouse splenic macrophages that captures antigen from the blood and transfers it to dendritic cells (DCs). In human and mouse spleen, we detected CD169⁺ cells at an equivalent location using immunofluorescence microscopy. Immunization with melanoma antigens conjugated to antibodies (Abs) specific for mouse CD169 efficiently induced gp100 and Trp2-specific T cell responses in mice. In HLA-A2.1 transgenic mice targeting of the human MART-1 peptide to CD169 induced strong MART-1-specific HLA-A2.1-restricted T cell responses. Human gp100 peptide conjugated to Abs specific for human CD169 bound to CD169-expressing monocyte-derived DCs (MoDCs) and resulted in activation of gp100-specific T cells. Together, these data indicate that Ab-mediated antigen targeting to CD169 is a potential strategy for the induction of melanoma-specific T cell responses in mice and in humans.

Comparison of Protein and Peptide Targeting for the Development of a CD169-Based Vaccination Strategy Against Melanoma.

CD169+ macrophages are part of the innate immune system and capture pathogens that enter secondary lymphoid organs such as the spleen and the lymph nodes. Their strategic location in the marginal zone of the spleen and the subcapsular sinus in the lymph node enables them to capture antigens from the blood and the lymph respectively. Interestingly, these specific CD169+ macrophages do not destroy the antigens they obtain, but instead, transfer it to B cells and dendritic cells (DCs) which facilitates the induction of strong adaptive immune responses. This latter characteristic of the CD169+ macrophages can be exploited by specifically targeting tumor antigens to CD169+ macrophages for the induction of specific T cell immunity. In the current study we target protein and peptide antigen as antibody-antigen conjugates to CD169+ macrophages. We monitored the primary, memory, and recall T cell responses and evaluated the anti-tumor immune responses after immunization. In conclusion, both protein and peptide targeting to CD169 resulted in strong primary, memory, and recall T cell responses and protective immunity against melanoma, which indicates that both forms of antigen can be further explored as anti-cancer vaccination strategy.