Immunomics analysis of rheumatoid arthritis identified precursor dendritic cells as a key cell subset of treatment resistance.

OBJECTIVES: Little is known about the immunology underlying variable treatment response in rheumatoid arthritis (RA). We performed large-scale transcriptome analyses of peripheral blood immune cell subsets to identify immune cells that predict treatment resistance. METHODS: We isolated 18 peripheral blood immune cell subsets of 55 patients with RA requiring addition of new treatment and 39 healthy controls, and performed RNA sequencing. Transcriptome changes in RA and treatment effects were systematically characterised. Association between immune cell gene modules and treatment resistance was evaluated. We validated predictive value of identified parameters for treatment resistance using quantitative PCR (qPCR) and mass cytometric analysis cohorts. We also characterised the identified population by synovial single cell RNA-sequencing analysis. RESULTS: Immune cells of patients with RA were characterised by enhanced interferon and IL6-JAK-STAT3 signalling that demonstrate partial normalisation after treatment. A gene expression module of plasmacytoid dendritic cells (pDC) reflecting the expansion of dendritic cell precursors (pre-DC) exhibited strongest association with treatment resistance. Type I interferon signalling was negatively correlated to pre-DC gene expression. qPCR and mass cytometric analysis in independent cohorts validated that the pre-DC associated gene expression and the proportion of pre-DC were significantly higher before treatment in treatment-resistant patients. A cluster of synovial DCs showed both features of pre-DC and pro-inflammatory conventional DC2s. CONCLUSIONS: An increase in pre-DC in peripheral blood predicted RA treatment resistance. Pre-DC could have pathophysiological relevance to RA treatment response.

[Ruptured pseudoaneurysm of the renal artery associated with segmental arterial mediolysis].

We present a 71-year-old woman with spontaneous perinephric hematoma due to a rupture of pseudoaneurysm of the right renal artery on the fourth day after radical cystectomy and bilateral ureterocutaneostomy for bladder cancer. This patient received steroid therapy for chronic rheumatoid arthritis for several years. The digital subtraction angiography of the right renal artery showed two pseudoaneurysms in the anterior inferior segmental branch and the posterior inferior segmental branch. Transarterial coil embolization of the right renal artery proximally and distally to the two aneurysms was performed without complications. Moreover, the additional angiography showed typical string-of-beads appearance and small aneurysms in abdominal visceral arteries, suggesting segmental arterial mediolysis (SAM) as a possible etiology. Differential diagnoses of SAM are discussed.

A Drug Utilization Study on Off-Label Uses / 薬剤疫学

Objective : Percutaneous ethanol injection (PEIT) for hepatocellular carcinoma is basic treatment of hepatocellular carcinoma. However, it is off-label uses to use ethanol for this treatment in the current state. Then, we executed the drug utilization study of Absolute ethanol injections at this time. <BR>Methods : We executed the drug utilization study of Absolute ethanol injections at this time. <BR>Results : The recovery of the questionnaire was high with 84.4% (151/179 medical institutions). The ethanol injections was made by 85% (129/151 facilities). Facilities where 100 or more ethanol injections was made annually were 76%. The raw material for making the ethanol injections was the reagent which was not the medicine in 44% of facilities. Information on safety and effectiveness concerning the ethanol injections was hardly offered from pharmacy. Finally, 96% (124/129 facilities) demanded marketing the ethanol injections. <BR>Conclusion : We investigated the research report number by using “ICHUSHI” CD-ROM version (1988-1998) which was the medical literature data base. We were able to collect reports concerning PEIT of hepatocellular carcinoma of 636 reports. We were able to collect reports which used PEIT as a treatment method of hepatocellular carcinoma by as many as 636 reports. It has been understood that PEIT is enforced in Japan. Next, we reviewed the document and collected and evaluated information on effectiveness and safety concerning the ethanol injections used for PEIT. The treatment object, the usage, and the dosage have been decided at the relating academic meeting. Moreover, there was a report concerning a lot of effectiveness and safety in the PEIT treatment method of hepatocellular carcinoma. The ethanol injections used for PEIT is one of the medicines where information and scientific evidence concerning effectiveness and safety are accumulated. Moreover, a large amount of ethanol injections are nationally made in the pharmacy in the hospital. However, it has been proved that there are a lot of problems about the making. The ethanol injections is the medicine which should be supplied and made by the pharmaceutical company.

A Drug Utilization Study on Off-Label Uses / 薬剤疫学

Objective : Heparin lock flush solution is diluctes and divided into vials before its use while it is used in quantity in Japan. Then, we carried out the research on use of heparin lock flush solution.<BR>Methods : We executed the nationwide questionnaire investigation concerning making heparin lock flush solution.<BR>Results : The recovery of the nationwide questionnaire investigation was as high as 78% (64/82) indicating general concern for the problem.<BR>Heparin lock flush solution was made in 97% (246/253) of wards. 69% (174/253) of wards had a standard for preparation. Therebon, it is thought that the standardization of heparin lock flush solution is possible. The use concentration employed most frequently for the peripheral intravenous injection was 10 units/ml and that for the central vein injection was 100/ml units. In many wards the amount used at 1 time for the peripheral intravenous injection was 5 ml or 10 ml and that for the central vein injection, was 5 ml, 10 ml, or 20 ml.<BR>84% of nurses requested marketing of heparin lock flush solution.<BR>Conclusion : We investigated the use realities and the problem of heparin lock flush solution from a past report etc. Heparin lock flush solution is listed to the pharmacopeia in the United States and Britain. Heparin lock flush solution should be supplied as the goods on the market immediately even if it is seen from the profit, the safety, the medical economy.