Clinical Rheumatology最新文献

Background: Rheumatoid arthritis (RA) could increase all-cause and cardiovascular mortality, particularly in elderly patients. Malnutrition is usually found in RA and contributes to poorer outcomes, with geriatric nutritional risk index (GNRI) serving as a dependable indicator to provide information on nutritional risk in elderly populations. We aim to elucidate connection between GNRI and survival outcomes in elderly RA patients.

Methods: Using NHANES database from 1999-2018, 1,473 RA patients ≥ 60 years old have been chosen. Participants were categorized into High-GNRI and Low-GNRI group with a threshold of 98. Mortal status was extracted from the Linked Mortality Files. Cox regression was utilized to further assess the relationship.

Results: Higher GNRI was significantly associated with lower all-cause (HR 0.563, 95% CI 0.423-0.751, p < 0.001) and cardiovascular mortality (HR 0.571, 95% CI 0.345-0.946, p = 0.030) in fully adjusted models, which was confirmed by Kaplan-Meier survival curves. Subgroup analyses further validated these associations across various demographic and clinical groups.

Conclusion: Higher GNRI is independently associated with a lower risk of all-cause and cardiovascular mortality in elderly RA patients, underscoring the importance of nutritional status in the survival of this population. Key Points • Higher GNRI was significantly associated with lower all-cause and cardiovascular mortality in elderly patients with rheumatoid arthritis. • Restricted cubic spline analysis revealed a linear association, with mortality risk decreasing as GNRI increased.

Objectives: To explore the association between serum vitamin D levels and the risk of knee and hip osteoarthritis (KOA and HOA).

Methods: This study included 295,557 participants (mean 56 years, 53% female) from the UK Biobank who had data on serum vitamin D levels and did not have KOA or HOA at baseline. The associations between serum vitamin D levels and the incidences of KOA and HOA were evaluated using Cox regression models. Mediating effects of serum biomarkers of inflammation (IL-1a, IL-1b, IL-6, and TNF) and cartilage metabolism (COMP, CRTAC1, and COL9A1) were explored.

Results: During a median follow-up of 13.1 years, 12,266 (4.2%) and 8931 (3.0%) participants developed KOA and HOA, respectively. Serum vitamin D levels were positively associated with osteoarthritis risk (KOA-hazard ratio [HR] = 1.14, 95% confidence interval [CI] 1.12-1.17; HOA-HR = 1.09, 95% CI 1.06-1.12). Compared to participants with severe vitamin D deficiency (< 25 nmol/L), those with sufficient vitamin D levels (≥ 75 nmol/L) had a 55% and 30% higher risk of developing KOA and HOA, respectively. Cartilage metabolism markers, but not inflammation markers, mediated 5.6%-12.6% of the associations between serum vitamin D levels and KOA risk.

Conclusion: High serum vitamin D levels are associated with an increased risk of OA in middle-aged and older adults. While serum vitamin D has recognized benefits for bone and cardiovascular health, these findings highlight a potential association with osteoarthritis risk without suggesting a causal effect. Key Points • High vitamin D levels increase osteoarthritis risk. • Cartilage metabolism partially mediates this association. • Inflammatory markers show no mediating effect.

Objective: The present study investigated the relationship between serum Matrix metalloproteinase-3 (MMP3) levels in Primary Sjögren's syndrome (pSS) patients and disease activity, clinical parameters, and different clinical manifestations of pSS.

Methods: Serum samples were obtained from 77 pSS patients and 77 healthy controls (HC). MMP3 levels were detected using a biochemical analyzer. Disease activity was assessed using the Sjögren's Syndrome Disease Activity Index (SSDAI) and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Pearson correlation analysis was employed to evaluate the relationship between MMP3 levels and clinical parameters.

Results: Serum MMP3 levels in pSS patients were significantly elevated compared to HC (P < 0.0001). Serum MMP3 levels were significantly positively correlated with WBC counts (r = 0.564, P < 0.0001), neutrophil counts (r = 0.5225, P < 0.0001), and serum LDH levels (r = 0.459, P < 0.0001). Moreover, MMP3 levels were significantly positively correlated with both SSDAI scores (r = 0.407, P = 0.002) and ESSDAI scores (r = 0.3061, P = 0.0068).

Conclusion: Serum MMP3 levels are significantly elevated in pSS patients and show significant positive correlations with both SSDAI and ESSDAI scores, as well as key inflammatory parameters (WBC, neutrophil counts, LDH). In conclusion, these consistent associations suggest the potential of serum MMP3 as a biomarker for tracking disease activity in pSS. Key Points • Serum MMP3 levels were significantly elevated in pSS patients. • Serum MMP3 levels showed strong associations with disease activity, WBC counts and neutrophil counts. • MMP3 may serve as a biomarker for tracking pSS activity.

Objective: Double-negative T cells (DNTs) are significantly elevated in autoimmune diseases and are thought to play an important role in inflammation. The purpose of this study was to explore their role in childhood-onset systemic lupus erythematosus (cSLE).

Methods: DNTs, as well as T and B cell subsets in peripheral blood, were detected by flow cytometry in 78 patients, including 34 cSLE. Clinical and laboratory data of cSLE patients were collected to analyze the correlation between DNTs and these indices, including demographics: proportion of female patients and mean age (± SD); Organ involvement: presence of lupus nephritis, neuropsychiatric manifestations, and pulmonary involvement; Hematologic parameters: leukopenia, anemia, and thrombocytopenia (WBC, Hb, and PLT counts); Autoantibody profiles: ANA, anti-dsDNA, and anti-Sm antibodies. The changes in DNT levels after glucocorticoid treatment were observed, and the effects of different doses of glucocorticoids on DNTs were analyzed.

Results: DNT levels were significantly increased in the peripheral blood of cSLE patients. DNTs were correlated with SLE disease activity, organ involvement, the production of autoantibodies, naive B cells, and plasmablasts. DNT levels increased after low-dose glucocorticoid treatment (9.12 ± 1.43 vs 14.24 ± 1.36, p < 0.01) but gradually decreased with increasing glucocorticoid doses (14.24 ± 1.36 vs 13.45 ± 1.51 vs 7.45 ± 1.01 vs 4.72 ± 1.20, p < 0.05). DNT levels significantly decreased from the fourth day of glucocorticoid pulse therapy.

Conclusion: DNT levels were positively correlated with disease activity in cSLE patients, and the effect of glucocorticoid dose on DNT levels varied. Key Points • DNT cells are significantly elevated in cSLE patients and correlate with disease activity, organ involvement, and autoantibody profiles. Low-dose glucocorticoids transiently increase circulating DNT levels, while higher doses progressively reduce DNT frequencies. DNT levels positively correlate with B-cell subsets, suggesting a potential role in autoantibody production in pediatric SLE. • Dynamic changes in DNTs may be influenced by glucocorticoid treatment.

Objective: This study aimed to elucidate the role of neuronaI precursor cell-expressed developmentally down-regulated 4-like (NEDD4L), a developmentally downregulated E3 ubiquitin ligase, in rheumatoid arthritis (RA).

Methods: Serum NEDD4L levels in RA patients (during both stable and active disease stages) and healthy controls were measured by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry (IHC) was used to analyze NEDD4L expression in synovial tissues from RA patients compared to traumatic control subjects. In animal experiments, the proteasome inhibitor MG-132 was administered to inhibit NEDD4L degradation, and its effects on joint inflammation and bone erosion were evaluated in a collagen-induced arthritis (CIA) rat model. At the cellular level, NEDD4L overexpression and knockdown models were constructed in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). The effects of NEDD4L on RA-FLS proliferation, migration, and invasion were assessed using CCK-8, wound healing and Transwell assays, respectively. Transcriptome analysis of the NEDD4L-knockdown model provided further insights into the associated diseases and pathways. Finally, the impact of NEDD4L on key proteins of the Wnt/β-catenin signaling pathway (DVL2, GSK3β, p-GSK3β, β-catenin) was examined via Western blotting and immunofluorescence, systematically investigating the mechanism of NEDD4L in RA pathogenesis both in vivo and in vitro.

Results: NEDD4L expression was downregulated in the serum and synovial tissues of RA patients. Functional assays demonstrated that NEDD4L knockdown enhanced the proliferative, migratory, and invasive capacities of RA-FLSs and promoted the secretion of the pro-inflammatory cytokines IL-6 and TNF-α, whereas NEDD4L overexpression exerted opposite effects. In CIA rats, MG-132 intervention alleviated joint inflammation and bone destruction, concomitant with restored synovial NEDD4L expression. Mechanistic studies further revealed that NEDD4L influences the biological behavior of RA-FLSs by regulating key components of the Wnt/β-catenin signaling pathway.

Conclusion: NEDD4L modulates the migration, invasion, and pro-inflammatory cytokine secretion of RA-FLSs via the Wnt/β-catenin signaling pathway, suggesting its potential as a therapeutic target for RA. Key Points • NEDD4L knockdown activates Wnt/β-catenin pathway (DVL2, GSK3β, β-catenin). • Promotes IL-6/TNF-α secretion and cell invasiveness. • NEDD4L overexpression shows opposite effects. • Potential therapeutic target for RA.

Objectives: This study aimed to investigate the prevalence of crystal arthritis in patients with unilateral knee effusion and to evaluate the diagnostic performance of US in comparison with radiography.

Methods: Patients above 18 years of age presenting with symptomatic unilateral knee effusion were included. Ultrasound of involved knees were performed. Hyperechoic bands within the femoral hyaline cartilage, hyperechoic foci in meniscal fibrocartilage, hyperechoic foci in the effusion and tendon calcifications were recorded as findings of calcium pyrophosphate dehydrate deposition(CPPD) disease and radiographic evaluations were done for searching chondrocalcinosis. SF aspiration was performed for searching crystals microscopically. Microscopic analysis accepted as the gold standard for CPPD, the sensitivity and specificity of US and radiography were assessed.

Results: Eighty-five patients with a mean age of 60.98 ± 11.95 years were included. None of them had uric acid crystals. CPPD was diagnosed with detecting CPP crystals in SF analysis in 15 of 85 patients. Two of these patients had coexisting rheumatoid arthritis (RA), 1 spondyloarthritis and 12 osteoarthritis. Of the remaining 70 patients, 1 was considered as spondyloarthritis, 4 as RA and 65 as exacerbation of osteoarthritis. The sensitivity and specificity of US were 93.33% and 80%, while radiography demonstrated values of 46.67% and 98.57%, respectively. Inter- and intra-rater agreement for US were 93.3% and 96.67%, respectively.

Conclusion: A notable 17.6% CPPD prevalence in patients with knee effusion suggests that this condition may be underestimated in practice due to diagnostic challenges. Ultrasound showed higher sensitivity than radiography, and specificity increased in parallel with the number of positive findings. Key Points • In detecting CPPD, ultrasound has higher sensitivity than radiography and specificity increases in parallel with the number of positive findings. • Ultrasound may provide additional diagnostic value when crystal detection with microscopic analysis is challenging.

Objective: Vasculitis often poses a significant burden on individuals, their families and the health care system. Understanding its epidemiology can aid in facilitating timely interventions. We present a province-wide population study comparing the 1) incidence of vasculitis amongst farmers, rural-non farmers and urban residents, 2) the use of health services and 3) all-cause mortality rates across the three cohorts.

Methods: The groups were randomly selected on the basis of provincial health data. Criteria for ascertaining vasculitis cases included either one hospital admission, two physician visits within a 2-year interval, or two ambulatory care visits within 2 years related to the vasculitis diagnosis. Descriptive statistics were used to compare the incidence rates.

Results: A total sample size of 302,089, with 5437 vasculitis cases. Farmers had the highest incidence of all types of vasculitis (109.8/100,000 person-years (PY)), followed by rural non-farmers (93.1/100,000 PY) and urbanites (71.7/100,000 PY). Age at diagnosis was higher among farmers (66.2 years) compared to rural non-farmers (64.5 years) and urbanites (63.9 years). Polymyalgia rheumatica (PMR) accounted for 47% of cases, followed by Arteritis Unspecified (15%) and small-vessel vasculitis (14%). Within the farming population, a higher percentage of males had positive cases of vasculitis compared to other populations. Rural non-farmer population had the highest use of health care services and unadjusted non-injury mortality rate (31.8/100,000 PY), followed by rural farmers (25.4/100,000 PY) and urban residents (23.8/100,000 PY).

Conclusion: Our province-wide study revealed that farmers face the highest incidence rates of vasculitis as well as the second highest burden of disease in terms of healthcare service needs and mortality. Key PointsAQ • There is a notable variation in the incidence rates of vasculitis among farmers, rural and urban residents with the farming population showing the highest incidence rate across most subtypes of vasculitis. • Farmers had a greater percentage of males diagnosed with vasculitis and an older age at diagnosis. • Rural non-farming patients with vasculitis demonstrate the highest utilization of healthcare services and mortality.

This study assessed the prevalence and clinical characteristics of Behçet's disease (BD) in the Middle East and North Africa (MENA) region, providing updated pooled estimates and identifying gaps in current epidemiological knowledge. We conducted a systematic review and meta-analysis of studies reporting the prevalence, epidemiology, or clinical features of BD in the MENA region, published in PubMed, MEDLINE, and Web of Science databases from 2014 onward. The eligible studies had observational designs and diagnoses based on internationally validated criteria. The study quality was assessed using the AXIS and MINORS tools. Pooled prevalence estimates and clinical feature proportions were calculated with 95% confidence intervals (CI); heterogeneity was quantified using I². Ten studies (sample size, 31-5218) from seven countries were included. The reported prevalence ranged from 0.06% in Turkey to 0.66% in Jordan. The pooled prevalence was 0.003 (300/100,000 population; 95% CI 0.001-0.005; p = 0.004) with a high heterogeneity (I² = 87.3%). No significant sex difference was observed in disease risk (odds ratio 1.55, 95% CI 0.59-4.05; p = 0.374). The pooled prevalence of major clinical features showed oral ulcers, genital ulcers, ocular involvement, and positive pathergy tests in 98.7%, 73.7%, 36.6%, and 54.6% of patients, respectively. BD prevalence in the MENA region remains among the highest worldwide. Clinical manifestations are consistent with global patterns but show regional variability, highlighting the need for standardized reporting, consistent epidemiological methodologies, and targeted strategies to support early diagnosis and recognition of the disease.

Objective: This study investigated the relationship between serum uric acid (SUA) levels and osteoporosis (OP) risk through cross-sectional and Mendelian randomization (MR) analyses to address the unclear role of SUA in bone metabolism.

Methods: Data from the 2015-2020 National Health and Nutrition Examination Survey were analyzed using multiple logistic regression, restricted cubic spline (RCS) modeling, and subgroup analyses. MR was performed using the inverse variance weighted method as the primary approach, complemented by diverse methods and sensitivity analyses.

Results: This study included 6,020 participants, of whom 1635 were diagnosed with OP. Based on the fully adjusted Model IV, individuals in the third (Q3) and fourth (Q4) quartiles exhibited a 38% (OR = 0.622; 95% CI: 0.423-0.915; P = 0.030) and 49% (OR = 0.513; 95% CI: 0.320-0.823; P = 0.015) lower risk of osteoporosis, respectively, relative to those in the lowest quartile (Q1) (Table 2). RCS analysis revealed an L-shaped inverse association (P-overall = 0.011; P-non-linear = 0.803) with a turning point around 5.3 mg/dL. Subgroup analysis suggested that sex, race, diabetes status, and serum cholesterol levels were potential effect modifiers (P-interaction < 0.05). MR analysis further demonstrated a significant causal protective effect of SUA levels on OP (OR = 0.870; 95% CI: 0.776-0.974, P = 0.016).

Conclusion: This study provides new evidence that higher SUA levels are associated with reduced risk of OP, offering potential implications for future preventive strategies. Key Points • Higher serum uric acid levels were independently associated with a lower risk of osteoporosis. • Gender, race, diabetes status, and serum cholesterol levels are factors that affect the negative association between serum uric acid and osteoporosis. • Mendelian randomization analysis supported a causal protective effect of serum uric acid levels on osteoporosis.