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ObjectivesTo compare look-locker inversion recovery (LLIR) and B1 inhomogeneity–corrected variable flip angle T1 mapping methods for estimation of liver function and prediction of hepatic insufficiency and decompensation on gadoxetic acid–enhanced MR imaging.MethodsIn this retrospective study, 248 patients with normal liver function, chronic liver disease, or cirrhosis underwent gadoxetic acid–enhanced liver MR imaging, including T1 mapping at 10-min and 20-min hepatobiliary phase (HBP) by using both methods. T1 relaxation times of the liver (T1Liver-pre, T1Liver-post) and the spleen (T1Spleen) were correlated between two methods. ΔT1Liver ([T1Liver-pre − T1Liver-post]/T1Liver-pre), adjusted T1Liver ([T1Spleen − T1Liver-post]/T1Spleen), and functional liver volume-to-weight ratio (liver volume on volumetric T1 map/[T1Liver-post × patient’s weight]) were calculated. The diagnostic performance of T1 parameters and the predictive performance of models (serum marker, serum marker plus T1 parameter) were compared.ResultsT1Liver-post showed a strong correlation (r = 0.93, p < 0.001) between two methods but was significantly different. For depicting cirrhosis, LLIR-adjusted T1Liver at 10-min HBP showed the highest performance (p < 0.025). For predicting hepatic insufficiency and decompensation, LLIR-adjusted T1Liver (Akaike information criterion (AIC), 58.37; C-index, 0.867) and LLIR-T1Liver-post (AIC, 48.82; C-index, 0.885) at 10-min HBP showed the best performance, respectively, when added to serum albumin level.ConclusionsT1Liver-post showed a strong correlation between two methods but with significant differences. T1 mapping using LLIR at 10-min HBP with obtainment of adjusted T1Liver and T1Liver-post may be the best approach for estimation of liver function and prediction of hepatic insufficiency and decompensation.Key Points• T1Liver-postshowed a strong correlation between LLIR and B1inhomogeneity–corrected VFA methods, both at 10-min and 20-min HBP but with significant differences.• T1Liver-postat 10-min and 20-min HBP using LLIR and B1inhomogeneity–corrected VFA methods could not be used interchangeably during the follow-up in patients with chronic liver disease (CLD) or cirrhosis.• T1 mapping using LLIR at 10-min HBP with obtainment of adjusted T1Liverand T1Liver-postmay be the most suitable method and parameter for estimation of global liver function and prediction of clinical outcomes in patients with CLD or cirrhosis.

Background Although the immunomodulatory properties of mesenchymal stem cells (MSCs) have been highlighted as a new therapy for autoimmune diseases, including rheumatoid arthritis (RA), the disease-specific characteristics of MSCs derived from elderly RA patients are not well understood. Methods We established MSCs derived from synovial fluid (SF) from age-matched early (average duration of the disease: 1.7 years) and long-standing (average duration of the disease: 13.8 years) RA patients (E-/L-SF-MSCs) and then analyzed the MSC characteristics such as stemness, proliferation, cellular senescence, in vitro differentiation, and in vivo immunomodulatory properties. Results The presence of MSC populations in the SF from RA patients was identified. We found that L-SF-MSCs exhibited impaired proliferation, intensified cellular senescence, reduced immunomodulatory properties, and attenuated anti-arthritic capacity in an RA animal model. In particular, E-SF-MSCs demonstrated cellular senescence progression and attenuated immunomodulatory properties similar to those of L-SF-MSC in an RA joint-mimetic milieu due to hypoxia and pro-inflammatory cytokine exposure. Due to a long-term exposure to the chronic inflammatory milieu, cellular senescence, attenuated immunomodulatory properties, and the loss of anti-arthritic potentials were more often identified in SF-MSCs in a long-term RA than early RA. Conclusion We conclude that a chronic RA inflammatory milieu affects the MSC potential. Therefore, this work addresses the importance of understanding MSC characteristics during disease states prior to their application in patients. Graphical abstract

The intricate connection between gut microbiota and rheumatoid arthritis (RA) pathogenesis has gained prominence, although the specific microbial species contributing to RA development remain largely unknown. Recent studies have sought to comprehensively explore alterations in the human microbiome, focusing on identifying disease-related microbial species through blood analysis. Consequently, this study aimed to identify RA-associated microbial species using a serum microbial array system and to investigate the efficacy and underlying mechanisms of potential microbial species for RA treatment. Serum immunoglobulin M levels against 384 intestinal microbial species were assessed using a microbial microarray in patients with RA and healthy individuals. We investigated the therapeutic potential of the identified microbial candidate regarding arthritis development, immune responses, gut barrier function, and gut microbiome using a collagen-induced arthritis (CIA) mouse model. Our findings revealed significant alterations in antibody levels against 36 microbial species in patients with RA compared to healthy individuals. Notably, the antibody levels against ( ) were decreased in patients with RA and exhibited an inverse correlation with RA disease activity. experiments demonstrated that produced acetate and butyrate, while exhibiting anti-inflammatory properties. In CIA mice, administration suppressed arthritis symptoms, reduced the accumulation of inflammatory monocytes in the mesenteric lymph nodes, and downregulated gene expression of pro-inflammatory cytokines in the ileum. Additionally, supplementation restored intestinal barrier integrity and partially resolved gut microbial dysbiosis in CIA mice. The fecal microbiota in -treated mice corresponded to improved intestinal barrier integrity and reduced inflammatory responses. This study highlights the potential of serum-based detection of anti-microbial antibodies to identify microbial targets at the species level for RA treatment. Moreover, our findings suggest that , identified through the microbial microarray analysis, holds therapeutic potential for RA by restoring intestinal barrier integrity and suppressing the immunologic response associated with RA.

Gout, a common form of inflammatory arthritis, is often managed with urate-lowering therapy, but many patients only adhere to treatment during gout attacks, resulting in poor follow-up and suboptimal management. This study aimed to identify characteristics associated with loss to follow-up (LTFU) and develop strategies for better patient management. Data were analyzed from the Urate Lowering TheRApy in gout (ULTRA) registry, a prospective cohort of Korean gout patients recruited since September 2021. Patients aged 18 or older who met the 2015 ACR/EULAR classification criteria were included. Demographic data, clinical characteristics, lifestyle habits, comorbidities, and quality of life assessments using the Korean Gout Impact Scale (K-GIS) and EuroQol 5-Dimension (EQ-5D) were collected at baseline, six months, and annually. LTFU was defined as missing a clinic visit for more than a year. Logistic regression was used to determine factors associated with LTFU. Among 269 patients, 125 (46.5%) were classified as LTFU. Patients not lost to follow-up experienced more frequent gout attacks (P = 0.020) and expressed greater concerns about future flares (P = 0.034). In contrast, LTFU patients had higher levels of anxiety (P = 0.049), depressive symptoms (P = 0.009), impaired mobility (P = 0.002), and a higher EQ-5D score (P = 0.002). Logistic regression identified frequent gout attacks, concerns about attacks, anxiety, impaired mobility, and EQ-5D scores as significant predictors of LTFU. Fewer gout attacks, heightened anxiety and depression, and lower quality of life were key factors associated with LTFU. Providing emotional support and comprehensive education may enhance follow-up and improve gout management.

To identify the prevalence of and risk factors for knee pain and radiographic knee osteoarthritis (RKOA) and to investigate the relationship between decreased lower extremity muscle mass (DLEM) and knee pain severity. Using data from the Korea National Health and Nutrition Examination Survey, 3,278 participants who were ≥50 years old and who underwent dual x-ray absorptiometry, plain knee radiographs and completed a knee pain questionnaire were enrolled. Lower extremity muscle mass (LEM) was defined as the sum of the fat-free soft tissue mass of the legs, and lower extremity muscle mass index (LMI) was calculated as LEM/body weight (%). DLEM was defined as an LMI more than two standard deviations below the mean of a gender-matched young reference group. Categorical variables were presented as numbers (weighted %). The prevalence of knee pain and RKOA were 22% (n = 721) and 34.7% (n = 1,234), respectively. Multivariate logistic regression analysis showed being female (OR 2.15, 95% CI 1.67-2.79), older (OR 1.03, 95% CI 1.01-1.04), less educated (OR 1.72, 95% CI 1.09-2.71), stiffness (OR 16.15, 95% CI 12.04-21.66), bed rest (OR 2.49, 95% CI 1.81-3.43), RKOA (OR 2.20, 95% CI 1.78-2.74) and DLEM (OR 1.54, 95% CI 1.09-2.17) were associated with knee pain. Participants with simultaneous RKOA and DLEM complained of more severe pain (pain score 7.18 ± 2.48) than those with knee pain without RKOA or DLEM (5.02 ± 2.44), those with only RKOA (6.29 ± 2.50), or those with only DLEM (6.78 ± 2.18) (P<0.001). These results remained after multivariate analyses of variance (MANOVAs). The prevalence of knee pain and RKOA were 22% and 34.7%, respectively, in the general Korean population. DLEM was an independent risk factor for knee pain and it was associated with increased pain severity, regardless of RKOA.

ObjectivesTo determine whether quantification of liver extracellular volume fraction (fECV) using dual-energy CT (DECT) allows prediction of liver-related events (LREs) in cirrhotic patients.MethodsThis retrospective study included 305 cirrhotic patients who underwent dual-source DECT imaging and had serum markers analyzed within 2 weeks of initial CT imaging. The fECV score was measured using an iodine map of equilibrium-phase images obtained 3 min after contrast injection at 100/140 Sn kVp. The association of the fECV score and serum markers with LREs was investigated. A risk model combining the fECV score (< 27 versus ≥ 27%) and serum albumin level (< 4 versus ≥ 4 g/dL) was constructed for LRE prediction.ResultsAn increased fECV score (odds ratio, 1.27; 95% confidence interval (CI), 1.15, 1.40) was independently associated with decompensated cirrhosis at baseline (n = 85) along with the Model for End-Stage Liver Disease score (odds ratio, 1.32; 95% CI, 1.07, 1.63). Among patients with compensated cirrhosis, 10.5% (23 of 220) experienced LREs during the median follow-up period of 2.0 years (decompensation, n = 14; hepatocellular carcinoma, n = 9). The fECV score (hazard ratio, 1.40; 95% CI, 1.22, 1.62) and serum albumin level (hazard ratio, 0.26; 95% CI, 0.09, 0.73) were independent predictors of LRE. The mean times to LRE among the high (16.5 months, n = 18)-, intermediate (25.6 months, n = 44)-, and low (30.5 months, n = 158)-risk groups were significantly different (p < 0.001).ConclusionsThe fECV score derived from DECT allows prediction of LREs in cirrhotic patients.Key Points• The extracellular volume fraction (fECV) score derived from the iodine map of dual-energy CT (DECT) was independently associated with the presence of hepatic decompensation.• The fECV score derived from the iodine map of DECT can predict liver-related events (LREs) in patients with cirrhosis.• Equilibrium-phase scanning in dual-energy mode is recommended as part of liver CT in cirrhotic patients because it can provide a prognostic indicator for LRE development.

Objective Insulin-like growth factor (IGF)-1 participates in modulating immunity and inflammation. Its bioactivity is controlled by six IGF-binding proteins (IGFBP-1 to IGFBP-6). In particular, the IGFBP-3 level is reportedly linked to the disease activity of rheumatoid arthritis (RA), consistent with our previous study. Therefore, the present study aimed to reproduce the previous results. Results The serum IGFBP-3 level was not significantly different among the three groups according to disease activity based on the DAS28-ESR/CRP ( p  > 0.05) but was significantly different between the low- and high-disease-activity groups based on the DAS28-CRP ( p  = 0.036). Meanwhile, the interleukin-6 (IL-6) level moderately correlated with DAS28-CRP (Spearman’s rho = 0.583, p  < 0.001).

SIRT1 modulates the acetylation of the p65 subunit of nuclear factor-κB (NF-κB) and plays a pivotal role in the inflammatory response. This study sought to assess the role of SIRT1 in rheumatoid arthritis (RA) using a myeloid cell-specific SIRT1 knockout (mSIRT1 KO) mouse. mSIRT1 KO mice were generated using the loxP/Cre recombinase system. K/BxN serum transfer arthritis was induced in mSIRT1 KO mice and age-matched littermate loxP control mice. Arthritis severity was assessed by clinical and pathological scoring. The levels of inflammatory cytokines in the serum and joints were measured by ELISA. Migration, M1 polarization, cytokine production, osteoclastogenesis, and p65 acetylation were assessed in bone marrow-derived monocytes/macrophages (BMMs). mSIRT1 KO mice showed more severe inflammatory arthritis and aggravated pathological findings than control mice. These effects were paralleled by increases in IL-1, TNF-α, TRAP-positive osteoclasts, and F4/80⁺ macrophages in the ankles of mSIRT1 KO mice. In addition, BMMs from mSIRT1 KO mice displayed hyperacetylated p65 and increased NF-κB binding activity when compared to control mice, which resulted in increased M1 polarization, migration, pro-inflammatory cytokine production, and osteoclastogenesis. Our study provides in vivo evidence that myeloid cell-specific deletion of SIRT1 exacerbates inflammatory arthritis via the hyperactivation of NF-κB signaling, which suggests that SIRT1 activation may be beneficial in the treatment of inflammatory arthritis.

Human adipose-derived stem cells (hADSCs) formed robust cell sheets by engineering the cells with soluble cell adhesive molecules (CAMs), which enabled unique approaches to harvest large area hADSC sheets. As a soluble CAM, fibronectin (FN) (100 pg/ml) enhanced the cell proliferation rate and control both cell-to-cell and cell-to-substrate interactions. Through this engineering of FN, a transferrable hADSC sheet was obtained as a free-stranding sheet (122.6 mm 2 ) by a photothermal method. During the harvesting of hADSC sheets by the photothermal method, a collagen layer in-between cells and conductive polymer film (CP) was dissociated, to protect cells from direct exposure to a near infrared (NIR) source. The hADSC sheets were applied to chronic wound of genetically diabetic db / db mice in vivo , to accelerate 30% faster wound closure with a high closure effect (ε wc ) than that of control groups. These results indicated that the engineering of CAM and collagens allow hADSC sheet harvesting, which could be extended to engineer various stem cell sheets for efficient therapies.