Effect of anaesthesia on cemented hemiarthroplasty -A multicentre retrospective study (TRON study).

INTRODUCTION: This study aimed to investigate the survival rate, postoperative complications, and walking ability in cemented hemiarthroplasty (HA) for displaced femoral neck fractures according to the anaesthesia method. METHODS: We conducted a retrospective study of a multicentre group (the TRON group). Three hundred fifty-eight patients who underwent cemented HA between 2015 and 2019 were selected; 289 patients of ≥75 years of age with no missing data were included. Patient background factors were matched and patients were assigned to spinal anaesthesia (SA) and general anaesthesia (GA) groups. The primary outcome was death at any time during the follow-up period. Secondary outcomes included postoperative complications and walking ability assessed using the Parker mobility score (PMS). Overall survival was evaluated using the Kaplan-Meier method, and differences were compared using the log-rank test. The incidence of each complication and PMS were compared between the two groups using Fisher's exact test. RESULTS: Overall survival during follow-up was significantly higher in the SA group in comparison to the GA group (p = 0.037). In the SA and GA groups, the survival rate at 3 months postoperatively was 98.4% and 95.5%, respectively. The incidence of postoperative pneumonia was significantly higher in the GA (p = 0.012), and PMS at 3 months postoperatively was significantly higher in the SA group (p = 0.016). CONCLUSION: The survival rate of elderly patients who underwent cemented HA was better in the SA group. General anaesthesia in cemented HA may be associated with lower life expectancy, increased incidence of pneumonia, and decreased walking ability.

Maitake α-glucan promotes differentiation of monocytic myeloid-derived suppressor cells into M1 macrophages.

AIMS: Myeloid-derived suppressor cells (MDSCs) are major components of the tumor microenvironment and systemically accumulate in tumor-bearing hosts and patients with cancer, facilitating cancer progression. Maitake macromolecular α-glucan YM-2A, isolated from Grifola frondosa, inhibits tumor growth by enhancing immune responses. The present study investigated the effects of YM-2A on the immunosuppressive potential of MDSCs. MAIN METHODS: YM-2A was orally administered to CT26 tumor-bearing mice, and the number of immune cells in the spleen and tumor was measured. Splenic MDSCs isolated from the CT26 tumor-bearing mice were treated with YM-2A and co-cultured with T cells to measure their inhibitory effect on T cell proliferation. For adoptive transfer of monocytic MDSCs (M-MDSCs), YM-2A-treated M-MDSCs mixed with CT26 cells were implanted subcutaneously in the mice to measure the tumor growth rate. KEY FINDINGS: YM-2A selectively reduced the accumulation of M-MDSCs but not that of polymorphonuclear MDSCs (PMN-MDSCs) in CT26 tumor-bearing mice. In tumor tissues, YM-2A treatment induced the polarity of immunostimulatory M1-phenotype; furthermore, it increased the infiltration of dendritic, natural killer, and CD4+ and CD8+ T cells. YM-2A treatment of purified M-MDSCs from CT-26 tumor-bearing mice induced dectin-1-dependent differentiation into M1 macrophages. YM-2A-treated M-MDSCs lost their inhibitory activity against proliferation and activation of CD8+ T cells. Furthermore, adoptive transfer of M-MDSCs treated with YM-2A inhibited CT26 tumor growth. SIGNIFICANCE: YM-2A promotes the differentiation of M-MDSCs into immunostimulatory M1 macrophages, thereby enhancing the efficacy of cancer immunotherapy.

Maturation of dendritic cells by maitake α-glucan enhances anti-cancer effect of dendritic cell vaccination.

Dendritic cells (DCs) play a primary role in antigen presentation to CD4+ and CD8+ T cells and induce acquired immune response against cancer cells. Therefore, determining positive modulators of DC activation to improve therapeutic approaches for cancer immunotherapy is greatly needed. In this study, we investigated the effect of maitake α-glucan YM-2A, isolated from Grifola frondosa, on the maturation and function of DCs and its adjuvant effect on a tumor-associated antigen (TAA)-loaded DC vaccine against murine tumor. We showed that YM-2A induced morphological changes and increased cell-surface maturation markers and cytokine production in DCs. In a mixed lymphocyte reactions assay, YM-2A-treated DCs increased proliferation and production of IFN-γ by allogeneic CD4+ and CD8+ T cells. These results indicate that YM-2A phenotypically and functionally activates DCs. Furthermore, YM-2A-treated TAA-loaded DC vaccine significantly reduced tumor growth and improved survival in two murine tumor models, CT-26 tumor-bearing BALB/c mice and B16 melanoma-bearing C57BL/6 mice. YM-2A-treated TAA-loaded DC vaccine increased splenic IFN-γ producing CD4+ and CD8+ T cells in CT-26 tumor-bearing BALB/c mice. Antibody neutralization studies indicated that YM-2A-induced DC maturation is mediated, in part, by the Dectin-1-dependent pathway. Overall, YM-2A-treatment with a TAA-loaded DC vaccine could be an excellent candidate for immunotherapy against cancer.

Antitumor activity of orally administered maitake α-glucan by stimulating antitumor immune response in murine tumor.

Maitake α-glucan, YM-2A, isolated from Grifola frondosa, has been characterized as a highly α-1,6-branched α-1,4 glucan. YM-2A has been shown to possess an anti-virus effect in mice; however, it does not directly inhibit growth of the virus in vitro, indicating that the anti-virus effect of YM-2A might be associated with modulation of the host immune system. In this study, we found that oral administration of YM-2A could inhibit tumor growth and improve survival rate in two distinct mouse models of colon-26 carcinoma and B16 melanoma. Orally administered YM-2A enhanced antitumor immune response by increasing INF-γ-expressing CD4+ and CD8+ cells in the spleen and INF-γ-expressing CD8+ cells in tumor-draining lymph nodes. In vitro study showed that YM-2A directly activated splenic CD11b+ myeloid cells, peritoneal macrophages and bone marrow-derived dendritic cells, but did not affect splenic CD11b- lymphocytes or colon-26 tumor cells. YM-2A is more slowly digested by pancreatic α-amylase than are amylopectin and rabbit liver glycogen, and orally administered YM-2A enhanced the expression of MHC class II and CD86 on dendritic cells and the expression of MHC class II on macrophages in Peyer's patches. Furthermore, in vitro stimulation of YM-2A increased the expression of pro-inflammatory cytokines in Peyer's patch CD11c+ cells. These results suggest that orally administered YM-2A can activate dendritic cells and macrophages in Peyer's patches, inducing systemic antitumor T-cell response. Thus, YM-2A might be a candidate for an oral therapeutic agent in cancer immunotherapy.

Enzymatic synthesis of unique sialyloligosaccharides using marine bacterial alpha-(2-->3)- and alpha-(2-->6)-sialyltransferases.

We investigated the acceptor substrate specificities of marine bacterial alpha-(2-->3)-sialyltransferase cloned from Photobacterium sp. JT-ISH-224 and alpha-(2-->6)-sialyltransferase cloned from Photobacterium damselae JT0160 using several saccharides as acceptor substrates. After purifying the enzymatic reaction products, we confirmed their structure by NMR spectroscopy. The alpha-(2-->3)-sialyltransferase transferred N-acetylneuraminic acid (Neu5Ac) from cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-Neu5Ac) to the beta-anomeric hydroxyl groups of mannose (Man) and alpha-Manp-(1-->6)-Manp, and alpha-(2-->6)-sialyltransferase transferred N-acetylneuraminic acid to the 6-OH groups of the non-reducing end galactose residues in beta-Galp-(1-->3)-GlcpNAc and beta-Galp-(1-->6)-GlcpNAc.