Clinical Rheumatology最新文献

Objectives: Despite extensive validation, the impact of medical comorbidities on the outcomes of the Hip Disability and Osteoarthritis Outcome Score (HOOS), Knee Injury Osteoarthritis Outcome Score (KOOS), and Foot and Ankle Outcome Score (FAOS) remains underexplored. This study aimed to evaluate the effect of medical comorbidities on HOOS, KOOS, and FAOS subscales using a large, nationally representative sample.

Methods: This national register-based cohort study invited 26,877 participants to complete HOOS, KOOS, or FAOS questionnaires. Medical comorbidities-including diabetes, chronic obstructive pulmonary disease/asthma, rheumatological diseases, osteoporosis, stroke, obesity, and heart disease-were identified through the Danish National Patient Register.

Results: A total of 7850 participants (29%) responded, with 1863 (24%) having medical comorbidities. HOOS/KOOS/FAOS subscale scores were significantly worse in patients with comorbidities, particularly in the Sport/Rec, ADL, and QOL subscales. Mean score differences between participants with and without comorbidities were pain (- 5.7, 95% CI - 6.6 to - 4.7), symptoms (- 4.6, 95% CI - 5.5 to - 3.6), ADL (- 7.1, 95% CI - 8.0 to - 6.1), Sport/Rec (- 10.4, 95% CI - 11.9 to - 8.9), and QOL (- 6.9, 95% CI - 8.2 to - 5.7). Diabetes, rheumatological diseases, and obesity were associated with the greatest complaints.

Conclusion: Patients with medical comorbidity reported significantly lower HOOS/KOOS/FAOS subscale scores compared to participants without medical comorbidity. Diabetes, chronic rheumatological diseases, and adiposities were observed with the most complaints. Key Points • Medical comorbidity predicts considerably lower HOOS/KOOS/FAOS subscale scores. • Diabetes, rheumatological diseases, and obesity exerted the most pronounced negative effects on the HOOS/KOOS/FAOS. • Findings underscore the importance of considering comorbidities when interpreting HOOS/KOOS/FOAS subscale scores.

Objective: Compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologics are more effective and are recommended to be included in the sequential treatment for psoriatic arthritis (PsA) patients. However, biologics are expensive and the cost-effectiveness of sequential biologic therapy in China remains unknown. The purpose of this study is to evaluate the cost-effectiveness of different sequential treatment option for PsA patients who have not responded to csDMARDs from the perspective of Chinese healthcare system.

Methods: We constructed a discrete event simulation model to evaluate the cost-effectiveness of 7 monotherapy treatments and 32 sequential treatments. In sequential therapy, two different types of biologics were used as first-line and second-line treatments, respectively, with the best supportive care (BSC) as the third-line treatment. The primary outcomes included total treatment costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way and probability sensitivity analyses were performed to explore the uncertainty of our model.

Results: Compared to all other strategies, initiating with secukinumab followed by etanercept (SEC-ETN) provided the highest health benefits. At a willingness-to-pay (WTP) threshold of US $38,161 per QALY, SEC-ETN was the most cost-effective strategy, with an ICER of $20,837 per QALY. One-way sensitivity analysis and probabilistic sensitivity analysis results confirmed the robust of this conclusion.

Conclusions: In China, SEC-ETN may be the most cost-effective strategy for patients who have failed treatment with csDMARDs and have not previously used biologics. The results provide evidence for identifying the optimal biologic treatment strategy for PsA patients in China. Key Points • Compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologics are more effective and are recommended to be included in the sequential treatment for psoriatic arthritis (PsA) patients. However, the cost-effectiveness of sequential biologic therapy in China remains unclear. • At a willingness-to-pay threshold of $38,161, initiating with secukinumab followed by etanercept (SEC-ETN) was cost-effective strategy, outperforming other strategies. • From the perspective of the Chinese healthcare system, the optimal biologic treatment strategy was SEC-ETN in China.

Objective: This systematic review aims to evaluate the efficacy and safety of various biological products, such as platelet-rich plasma (PRP), hyaluronic acid (HA), and combination treatments, in alleviating pain and improving function in patients with hip osteoarthritis (OA).

Methods: Our review followed the PRISMA guidelines. Literature was searched in PubMed, Scopus, Embase, Web of Science, and CENTRAL Cochrane databases from the beginning until July 2022 hinged upon the previously designed search strings, and citations were downloaded. We included randomized controlled trials (RCTs) involving patients over 18 years old with hip OA, comparing biological products to placebo or other interventions. Data were collected on pain, hip range of motion, functional status, quality of life, and radiological outcomes. Meta-analysis was done on the above-listed outcomes.

Results: From 18 RCTs involving 1648 patients, we analyzed the efficacy of various biological products. The mean age of patients was 60.2 years (SD 2.4), and the mean follow-up period was 7.22 months. PRP and HA treatments showed no statistically significant differences in VAS scores in the short-term (SMD = - 0.49, 95% CI, - 1.34-0.36), mid-term (SMD = - 0.25, 95% CI - 1.64-1.15), and long-term (SMD = - 0.22, 95% CI - 1.57-1.12) follow-ups. However, significant differences were found in WOMAC pain short-term (SMD = 0.40, 95% CI - 0.06-0.87), mid-term (SMD = 0.49, 95% CI - 0.85-1.83), and long-term outcomes (SMD = - 0.42, 95% CI - 0.80 to - 0.04). Complications were observed in HA (8%), Hylan G-F (4.9%), and GP-C (50%) groups, while PRP and BCC did not report any complications.

Conclusion: Our meta-analysis indicates that biological products, particularly PRP and HA, provide varying degrees of pain relief and functional improvement in hip OA patients, with a generally acceptable safety profile. The significant heterogeneity among studies underscores the need for further research to establish standardized treatment protocols and long-term efficacy.

Trial registration: CRD42022312562.

Introduction/objectives: Anti-Sjögren's syndrome A (SSA/Ro60) and anti-Sjögren's syndrome B (SSB/La) antibodies are not present in up to 25% of patients with primary Sjögren's disease (SjD). Our observational study aims to provide a clinical perspective on the presentation, extra-glandular manifestations, as well as the immune profile of anti-SSA/SSB antibody double-negative SjD patients.

Method: A total of 615 SjD patients of age 53.21 (± 0.59) were enrolled without acute infection or ongoing treatment that could affect the immune system. Of our participants, 254 (41.3%) were seronegative for both SSA (Ro60) and SSB (La) autoantibodies (SSA/SSB double-negative). A 1:1 propensity score matching was performed to balance age at diagnosis, disease duration, and gender for extra-glandular involvement analyses and immune profiling. Peripheral blood mononuclear cells (PBMCs) were derived from all patients. Flow cytometry was performed to further define the immune cell subsets.

Results: Our study revealed that anti-SSA/SSB seronegative patients had a delayed onset by an average of 7.43 years and exhibited a lower prevalence of parotid gland enlargement compared to the seropositive group (50.8% vs. 59%, p < 0.05). In terms of extra-glandular involvement, seronegative patients exhibited a lower prevalence of white blood cell (WBC), hemoglobin (HGB), and platelet (PLT) reduction (OR 0.406, 95% CI 0.314-0.523; OR 0.751, 95% CI 0.587-0.959; OR 0.56, 95% CI 0.383-0.818, respectively) compared to anti-SSA/SSB antibody-positive group. Additionally, the double-negative group tended to hold higher CD4 + T helper cells and lower CD8 + T cell proportions compared with the anti-SSA/SSB-positive group (40.52% vs. 37.38%, p < 0.001; 28.25% vs. 32.55%, p < 0.001 respectively). Higher proportions of NK cells (13.05% vs. 10.32%, p < 0.001) and CD161 + Treg cells (13.69% vs. 12.03%, p < 0.001) were found in the double-negative group.

Conclusion: The observed higher frequency of CD161 + Tregs and NK cells, as well as the lower frequency of CD8 + T cells and B cells, in anti-SSA/SSB antibody double-negative patients suggests a potential role of innate immunity in this subgroup of Sjögren's syndrome. Our findings hint at the importance of serological and immune profiles in tailoring personalized management strategies for these patients. Key Points • Our analyses suggested a potential role of innate immunity in anti-SSA/SSB antibody double-negative SjD patients in comparison to seropositive counterparts. • Higher frequencies of CD4 + T cells, CD161 + Tregs, and NK cells were observed in the peripheral blood of double-negative patients, alongside lower proportions of CD8 + T cells and B cell subsets. • Double-negative patients exhibited a lower prevalence of reductions in white blood cell counts, hemoglobin level, and platelet level.

Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease linked with metabolic dysfunction-associated steatotic liver disease (MASLD), which may increase cardiovascular (CV) risk. This study explores the association between liver fibrosis, assessed by the Fibrosis-4 (FIB-4) index, and CV risk factors in RA patients.

Methods: Cross-sectional data from the Franciscus Rheumatoid Arthritis and Cardiovascular Intervention Study (FRANCIS), a randomized, cardiovascular single center, intervention study involving RA patients without cardiovascular disease (CVD) or type 2 diabetes (T2DM), were analyzed. Liver fibrosis was assessed using FIB-4, with a cut-off point of ≥ 1.3 to define high fibrosis risk, and its relationship with CV risk factors, medication use, and subclinical atherosclerosis, measured by carotid intima-media thickness (cIMT), was evaluated.

Results: Among 326 patients (68.4% female, age 53 ± 11 years, BMI 26.5 ± 4.5 kg/m²), those with high FIB-4 (n = 49) had higher cIMT (p = 0.002), apolipoprotein B48 (p = 0.04), systolic blood pressure (p = 0.007), alkaline phosphatase (p = 0.002), and anti-CCP levels (p = 0.02). High FIB-4 was associated with lower leukocyte count and complement component 3. Statin use was linked to higher FIB-4 (OR = 4.49, p = 0.014), while hydroxychloroquine use was associated with lower FIB-4 (OR = 0.11, p = 0.004). Disease activity scores did not differ between low and high FIB-4 groups.

Conclusions: Elevated FIB-4 in RA patients is associated with increased cIMT, higher blood pressure, and elevated atherogenic remnants. Incorporating FIB-4 measurements into routine clinical care for RA populations could effectively identify individuals at the highest CV risk, enabling the implementation of more intensive CV risk management strategies. Key Points • RA patients with liver fibrosis have higher cIMT, indicating greater risk of atherosclerosis. • RA patients with liver fibrosis show accumulation of circulating atherogenic chylomicron remnants, contributing to atherogenesis. • HCQ may provide a protective effect against liver fibrosis in RA patients.

Objectives: Systemic sclerosis complicated with interstitial lung disease (SSc-ILD) is a rare autoimmune disease with a dismal prognosis. To analyze the common clinical indicators of systemic sclerosis (SSc) complicated with severe interstitial lung disease (ILD) patients based on the grading of lung high-resolution computed tomography (HRCT) and to explore the risk factors of severe (ILD).

Methods: A retrospective analysis was performed on 72 newly diagnosed and treated SSc-ILD patients in the Affiliated Hospital of Xuzhou Medical University from June 2013 to August 2023. The interstitial lung disease was divided into grades 1, 2, and 3 according to the HRCT images. Grades 1 and 2 were classified as a non-severe group (42 cases), and grade 3 was a severe group (30 cases). The general data and laboratory examination results of the two groups were analyzed. A logistic regression model was established, and the receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of risk factors for severe SSc-ILD patients.

Results: Patients in the severe group had lower height (1.610 ± 0.059 vs 1.574 ± 0.078, P = 0.031), triglyceride (TG) (1.796 ± 0.743 vs 1.265 (1.04, 1.63), P = 0.026) and total protein (TP) (77.96 ± 8.784 vs 72.709 ± 8.042, P = 0.011)than those in the non-severe group. The area under the curve of height, TG, and TP combined with the diagnosis of systemic sclerosis complicated with severe interstitial lung disease was 0.839, and the sensitivity and specificity were 0.750 and 0.781, respectively.

Conclusion: Low TG and TP may be the risk factors for SSc patients with severe interstitial lung disease. Therefore, it is promising as a potential therapeutic target for SSc-ILD and warrants appropriate follow-up in further studies of patients. Key Points • We hoped to pay attention to the influence of metabolic factors on connective tissue disease complicated with interstitial lung disease due to the relationship between metabolism and immunity is complicated.

Objective: The macrophage migration inhibitory factor (MIF) in the plasma, hydrops articuli, and synovium, and its relationship with laboratory indexes in patients with rheumatoid arthritis (RA) were determined, for the purpose to reveal the role of MIF on the pathogenesis of RA.

Methods: MIF mRNA expression in PBMCs was detected by qPCR. Plasma MIF was measured by enzyme linked immunosorbent assay (ELISA). MIF in hydrops articuli and synovium from RA patients and OA patients was evaluated by immunofluorescence (IF) and immunohistochemistry (IHC). The relationship between MIF and laboratory indexes of RA patients was analyzed. Human fibroblast-like synoviocytes (FLS) were treated with recombinant human MIF, and expression of inflammatory factors was determined by qPCR. The matrix metalloproteinase (MMP) 9 and extracellular regulated protein kinases (ERK)1/2 in FLS with MIF treatment were detected.

Results: MIF is significantly increased in plasma and hydrops articuli in RA patients. The expression of multiple inflammatory factors and MMPs was increased in RA patients and in FLS with rhMIF treatment. MIF was correlated with laboratory indexes in RA patients. Mechanistically, MIF promoted production of MMP9 by FLS through the ERK1/2 pathway.

Conclusion: Our results indicated that increased MIF was correlated with disease activity of RA patients. These findings also suggested that MIF induced multiple inflammatory factors and MMP 9 in FLS via ERK 1/2 pathway. Key Points • MIF plays a key role in the initiation of RA by promoting the expression of various inflammatory factors in FLS and MMPs. • This study provides a basis for MIF-targeted RA clinical therapy and for exploring the feasibility of MIF as a therapeutic target for RA. • Increased MIF correlates with disease activity in RA patients.

Introduction: IgA vasculitis (IgAV) can present as skin-limited or systemic disease, which can be severe in adults. Predictive markers for visceral involvement are suboptimal. Considering haptoglobin's role as an acute phase reactant, we evaluated whether its differential expression in IgAV patients' skin and leukocytes is also reflected systemically in a larger cohort of adult IgAV patients. Additionally, soluble form of haptoglobin scavenger receptor CD163 was measured in IgAV patient serum.

Methods: We re-analyzed RNA sequencing data from leukocytes and skin biopsies of treatment-naïve adult IgAV patients: (1) IgAV nephritis (n = 3), (2) skin-limited IgAV (n = 3), and healthy controls (n = 3). Haptoglobin serum level was measured in 178, and haptoglobin genotyping was performed in 91 treatment-naïve adult IgAV patients. Serum sCD163 was measured in 60 IgAV patients and 22 HC.

Results: Transcriptomic data of leukocytes and skin of IgAV nephritis patients identified haptoglobin as a hub gene, based on protein-protein interaction network. Haptoglobin serum level was elevated in IgAV patients with nephritis or gastrointestinal involvement compared to other IgAV patients. Patients who relapsed during follow-up had decreased haptoglobin serum level at disease presentation compared to non-relapsing patients. Haptoglobin genotyping did not show differences between genotype groups regarding clinical presentation and laboratory parameters. Serum sCD163 was significantly higher in IgAV nephritis patients compared to HC.

Conclusion: We identified haptoglobin as a novel marker of visceral involvement and relapse in adult IgAV, while sCD163 is linked to renal involvement. Further studies will confirm the clinical utility of haptoglobin as biomarker in IgAV. Key Points • Haptoglobin expression is upregulated in leukocytes and skin of adult IgAV with renal involvement. • Haptoglobin serum level is elevated in IgAV patients with visceral involvement. • Patients with IgAV relapse have lower haptoglobin at disease presentation.