Gene Expression Profiling to Unfolded Proteins Response as a Risk Modulator of Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Despite new methods of diagnostics and treatment as well as extensive biological and immunosuppressive treatment, the etiology of RA is not fully understood. Moreover, the problem of diagnosis and treatment of RA patients is still current and affects a large group of patients. It is suggested that endoplasmic reticulum (ER)-related features may impair adaptation to chronic stress, inferring the risk of rheumatoid arthritis. The main goal in this study was evaluation of changes in mRNA translation to determine chronic ER stress conditions in rheumatoid arthritis patients. The study group consist of 86 individuals including a total of 56 rheumatoid arthritis patients and 30 healthy controls. The expression level of mRNA form blood samples of RA patients as well as controls of the unfolded protein response (UPR)-associated genes (p-eIF2, BCL-2, PERK, ATF4, and BAX) were investigated using real-time qPCR. GAPDH expression was used as a standard control. Considering the median, the expression levels of PERK, BCL-2, p-eIF2, ATF4, and BAX were found to be significantly increased in the blood of RA patients compared with the control group. The p-value for the PERK gene was 0.0000000036, the p-value for the BCL-2 gene was 0.000000014, the p-value for the p-eIF2 gene was 0.006948, the p-value for the ATF4 gene was 0.0000056, and the p-value for the BAX gene was 0.00019, respectively. Thus, it can be concluded that the targeting of the components of the PERK-dependent UPR signaling pathway via small-molecule PERK inhibitors may contribute to the development of novel, innovative treatment strategies against rheumatoid arthritis.

Cloverleaf Sign in Pelvic Magnetic Resonance Imaging for Deep Infiltrating Endometriosis: Association With Longer Operation Times, Greater Blood Loss, and Higher Rates of Bowel Resection.

OBJECTIVES: The aim of this study was to evaluate the significance of a new imaging sign, the "cloverleaf sign," in diagnosing deep infiltrating endometriosis (DIE) with magnetic resonance imaging (MRI) in concordance to intraoperative findings. MATERIALS AND METHODS: This retrospective study included 103 patients operated during the January 2016 to June 2018 period with preoperative 1.5 T and 3 T MRI, with or without vaginal and rectal gel filling. Magnetic resonance imaging scans were read blinded to intraoperative findings by a specialized gynecologic radiologist and a junior radiologist, and then compared with intraoperative findings by looking at the operation report, postoperative diagnosis, and intraoperative images and videos by an experienced gynecologist surgeon specialized in endometriosis surgery. All endometriosis lesions were confirmed by pathology. The "cloverleaf sign" was defined as a cloverleaf-like figure in imaging morphology; the "leaves" formed by at least 3 different organs come together in the center of the figure formed by constrictive adhesions including T2-weighted (T2W) hypointense DIE. Operation times, intraoperative blood loss, and the frequency of DIE and bowel resections were analyzed in cloverleaf and noncloverleaf groups. The 2-sample Wilcoxon rank-sum (Mann-Whitney U) test and multivariate analysis of variance were used to calculate the significance of an overall impact of cloverleaf sign on operation time, blood loss, and the amount of the bowel resection rate. P < 0.05 was considered statistically significant. RESULTS: The prevalence of DIE in the study population was 79.6%. A total of 11.5% of the patients had no endometriosis, 32.6% had rASRM I and II, and 55.9% had rASRM III and IV. Forty-six patients (45%) had received rectal and vaginal gel opacification before scanning, 57 (55%) did not. A cloverleaf sign on MRI was detected in 34 patients (15 in gel filling and 19 in nonfilling group). The interreader agreement was almost perfect 0.91 (κ). The median operation time in the cloverleaf group was 248 minutes (interquartile range [IQR], 165-330) compared with 145 minutes in the noncloverleaf group (IQR, 90-210), that is, significantly higher (P < 0.001). Intraoperative blood loss was also significantly higher in the conglomerate group (125 vs 50 mL; IQR, 100-300 vs 50-100; P < 0.001). Of the bowel resections in our study population, 41% (14/34) were performed on patients with a cloverleaf sign in the MRI, compared with 13% (9/69) in patients without the cloverleaf sign. CONCLUSIONS: The "cloverleaf" MRI sign was associated with significantly longer operation time, increased intraoperative blood loss, and higher rates of bowel resection in DIE patients.