The goal of the present meta-analysis was to identify factors that contribute to P300 event-related brain potential (ERP) differences in patients with schizophrenia compared to unaffected controls in an attempt to characterize the clinically relevant dimensions underlying P300 deficits in patients with schizophrenia. P300 effect size (d) was smaller in amplitude and longer in latency in schizophrenic patients compared to normal controls, with the strongest effects obtained from the auditory oddball. Paranoid subtype demonstrated larger P300 amplitude effect sizes than other disease subtypes, and P300 latency effect size decreased with disease duration. Psychopathology severity and antipsychotic medications were unrelated to P300 amplitude effect size. Gender proportion, educational level, and stimulus and task variables also affected P300 amplitude and latency effect sizes. The findings are used to formulate a theoretical account of the empirical data and provide suggestions for maximizing the utility of the P300 component in the assessment of schizophrenia.

Hemophagocytic lymphohistiocytosis is an overwhelming systemic inflammatory process that is life-threatening if not treated appropriately. We analyzed prognostic factors of secondary hemophagocytic lymphohistiocytosis excluding malignancy. In this retrospective study, we analyzed 126 adult cases between 2001 and 2017. Treatment was based on dexamethasone with or without etoposide and cyclosporine. Patients who achieved complete response at 4 weeks were defined as early-stable responders, those who failed to achieve complete response but showed continuous improvement until 8 weeks as late responders, those whose conditions waxed and waned until 8 weeks as unstable responders. Patients with hemophagocytic lymphohistiocytosis caused by Epstein-Barr virus experienced worse 5-year overall survival compared to autoimmune disease, other infections, and unknown causes (25.1% vs. 82.4%, 78.7%, 55.5%, p<0.001). We observed that overall response rate at 4 weeks was similar, but decreased at 8 weeks in the Epstein-Barr virus subgroup from 75.5% to 51.0%, and finally decreased to 30.6%. Multivariate analysis revealed that 8-week treatment response was the most relevant factor for overall survival. Excluding 8-week response, Epstein-Barr virus, old age, hyperferritinemia, and thrombocytopenia were associated with poor survival. We established a prognostic model with the parameters: low-risk (score 0-1), intermediate-risk (score 2), and high-risk (score≥3). These groups had 5-year overall survival of 92.1%, 36.8%, and 18.0%, respectively (p<0.001). We found that 8-week treatment response was a good predictive factor for overall survival, and that Epstein-Barr virus, old age, thrombocytopenia, and hyperferritinemia were associated with poor survival outcomes. Physicians should take care to identify high-risk patients for appropriate treatment strategies.

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Mesenchymal stem cells (MSCs) possess immunomodulatory properties and have potential, however, there have been conflicting reports regarding their effects in rheumatoid arthritis (RA), which causes inflammation and destruction of the joints. Through a comparative analysis of regulatory T (Treg) and IL-10-producing type 1 regulatory T (Tr1) cells, we hypothesized that Tr1 cells enhance the immunoregulatory functions of MSCs, and that a combinatorial approach to cell therapy may exert synergistic immunomodulatory effects in an experimental animal model of rheumatoid arthritis (RA). A combination of MSCs and Tr1 cells prevented the development of destructive arthritis compared to single cell therapy. These therapeutic effects were associated with an increase in type II collagen (CII)-specific CD4+CD25+Foxp3+ Treg cells and inhibition of CII-specific CD4+IL-17+ T cells. We observed that Tr1 cells produce high levels of IL-10-dependent interferon (IFN)-β, which induces toll-like receptor (TLR) 3 expression in MSCs. Moreover, induction of indoleamine 2,3-dioxygenase (IDO) by TLR3 involved an autocrine IFN-β that was dependent on STAT1 signaling. Furthermore, we observed that production of IFN-β and IL-10 in Tr1 cells synergistically induces IDO in MSCs through the STAT1 pathway. These findings suggest co-administration of MSCs and Tr1 cells to be a novel therapeutic modality for clinical autoimmune diseases.