OBJECTIVE: To explore, identify, and develop novel blood-based indicators using machine learning algorithms for accurate preoperative assessment and effective prediction of postoperative complication risks in patients with rheumatoid arthritis (RA) undergoing total knee arthroplasty (TKA). METHODS: A retrospective cohort study was conducted including RA patients who underwent unilateral TKA between January 2019 and December 2024. Inpatient and 30-day postoperative outpatient follow-up data were collected. Six machine learning algorithms, including decision tree, random forest, logistic regression, support vector machine, extreme gradient boosting, and light gradient boosting machine, were used to construct predictive models. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), F1-score, accuracy, precision, and recall. SHapley Additive exPlanations (SHAP) values were employed to interpret and rank the importance of individual variables. RESULTS: According to the inclusion criteria, a total of 1 548 patients were enrolled. Ultimately, 18 preoperative indicators were identified as effective predictive features, and 8 postoperative complications were defined as prediction labels for inclusion in the study. Within 30 days after surgery, 453 patients (29.2%) developed one or more complications. Considering overall accuracy, precision, recall, and F1-score, the random forest model [AUC=0.930, 95% CI (0.910, 0.950)] and the extreme gradient boosting model [AUC=0.909, 95% CI (0.880, 0.938)] demonstrated the best predictive performance. SHAP analysis revealed that anti-cyclic citrullinated peptide antibody, C-reactive protein, rheumatoid factor, interleukin-6, body mass index, age, and smoking status made significant contributions to the overall prediction of postoperative complications. CONCLUSION Machine learning-based models enable accurate prediction of postoperative complication risks among RA patients undergoing TKA. Inflammatory and immune-related blood biomarkers, such as anti-cyclic citrullinated peptide antibody, C-reactive protein, and rheumatoid factor, interleukin-6, play key predictive roles, highlighting their potential value in perioperative risk stratification and individualized management.
Humans ; Arthroplasty, Replacement, Knee/adverse effects* ; Arthritis, Rheumatoid/blood* ; Machine Learning ; Postoperative Complications/blood* ; Female ; Male ; Retrospective Studies ; Middle Aged ; Aged ; Risk Factors ; Preoperative Period ; C-Reactive Protein/analysis* ; Risk Assessment

OBJECTIVE: To explore the potential causal relationship between intervertebral disc degeneration and certain autoimmune diseases. METHODS: Genome-wide association study (GWAS) data of 5 autoimmune diseases were obtained from large-scale GWAS databases. Data on internal vertebral disc degeneration (IVDD) were derived from the FinnGen consortium, which included 294, 770 controls and 41, 669 cases. A two-sample bidirectional Mendelian randomization (MR) analysis was performed to investigate the potential causal relationship between the 5 autoimmune diseases and IVDD. Multiple analytical methods were adopted, including MR methods such as inverse variance weighting(IVW), MR-Egger, weighted median, weighted mode, and simple mode. Cochran's Q test, leave-one-out analysis, and MR-Egger intercept test were conducted to assess heterogeneity, robustness, and pleiotropy. For the robustness of the results, MR-PRESSO was used to detect outliers, and MR analysis was re-conducted after removing the outliers. RESULTS: The MR analysis results showed that there might be a bidirectional causal relationship between ankylosing spondylitis(AS) and IVDD:AS on IVDD, OR=1.038, 95%CI (1.024, 1.053), P=0.000;and IVDD on AS, OR=2.117, 95%CI(1.065, 4.207), P=0.032. There might be a positive correlation between IVDD and rheumatoid arthritis(RA) as well as systemic lupus erythematosus(SLE):IVDD on RA, OR=1.184, 95%CI(1.071, 1.309), P=0.001;and IVDD on SLE, OR=1.678, 95%CI(1.187, 2.372), P=0.003. There was no significant correlation between ulcerative colitis(UC), autoimmune thyroiditis(ATD) and IVDD. After removing outliers by MR-PRESSO and re-conducting MR analysis, the results did not change qualitatively. Sensitivity analysis indicated that the results were robust to potential sources of bias. CONCLUSION AS and IVDD may be risk factors for each other, and IVDD may be a potential risk factor for RA and SLE. These findings provide a basis for guiding the prevention and combined diagnosis and treatment of IVDD, AS, RA, and SLE, while the specific underlying mechanisms still require further experimental basic research.
Humans ; Intervertebral Disc Degeneration/etiology* ; Mendelian Randomization Analysis ; Autoimmune Diseases/complications* ; Genome-Wide Association Study ; Spondylitis, Ankylosing/genetics* ; Arthritis, Rheumatoid/genetics*

Rheumatoid arthritis (RA), an autoimmune disease characterized by chronic inflammation of synovial tissue, is divided into two subtypes-anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA. While the pathogenic mechanisms of ACPA-positive RA are well-understood, the etiology of ACPA-negative RA remains largely unknown. The association between RA and periodontitis (PD) has been observed since the early 1900s, with the two diseases sharing common genetic and environmental risk factors that lead to the progressive destruction of bone and connective tissue. However, the associations between PD and the two subtypes of RA differ. This comprehensive review aims to provide an updated understanding of the epidemiological association between RA and PD, explore potential pathogenic mechanisms linking the two diseases, and highlight the key distinctions between the subtypes of RA and their respective associations with PD. We also discuss the possibility of early intervention or the treatment of the two diseases. Ultimately, this review aims to provide valuable insights for future research in this field.
Humans ; Arthritis, Rheumatoid/complications* ; Periodontitis/complications* ; Anti-Citrullinated Protein Antibodies/immunology* ; Risk Factors

OBJECTIVES: To investigate the causal associations between autoimmune diseases and aplastic anemia (AA) using Mendelian randomization analysis. METHODS: Publicly available genome-wide association study (GWAS) data were utilized to obtain single nucleotide polymorphisms (SNPs) associated with autoimmune diseases and AA for analysis. The inverse variance weighted (IVW) method was employed as the primary analytical approach, with MR Egger, Weighted Mode, Weighted Median, and Simple Mode methods serving as complementary analyses. Heterogeneity and pleiotropy analyses were conducted using designated functions, and the robustness of Mendelian randomization results was assessed using leave-one-out analysis. RESULTS: The two-sample Mendelian randomization analysis using the IVW method revealed significant positive causal associations of rheumatoid arthritis (OR=1.094, 95% CI: 1.023-1.170, P=0.009, adjusted P=0.042), systemic lupus erythematosus (OR=1.111, 95% CI: 1.021-1.208, P=0.015, adjusted P=0.036), Hashimoto thyroiditis (OR=1.206, 95% CI: 1.049-1.387, P=0.009, adjusted P=0.029), and Sicca syndrome (OR=1.173, 95% CI: 1.054-1.306, P=0.004, adjusted P=0.035) with AA, which was supported by the results from the Weighted Median method. Sensitivity analyses indicated no evidence of pleiotropy or heterogeneity, and leave-one-out analysis confirmed the robustness of the causal relationships. No direct evidence was found linking Graves' disease, ulcerative colitis, Crohn's disease, autoimmune hepatitis, primary biliary cholangitis, or primary sclerosing cholangitis with AA (P>0.05, adjusted P>0.05), indicating a lack of causal association. Reverse Mendelian randomization results and multiple corrections indicated that AA was not an influencing factor for autoimmune diseases (adjusted P>0.05). CONCLUSIONS Our findings support at the genetic level that rheumatoid arthritis, systemic lupus erythematosus, Hashimoto thyroiditis, and Sicca syndrome are risk factors for AA, and confirm a causal association of the these 4 autoimmune diseases with an increased risk of AA.
Humans ; Mendelian Randomization Analysis ; Anemia, Aplastic/genetics* ; Autoimmune Diseases/complications* ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Arthritis, Rheumatoid/genetics* ; Lupus Erythematosus, Systemic/genetics* ; Genetic Predisposition to Disease

INTRODUCTION: Rheumatoid arthritis (RA) is associated with heightened cardiovascular disease and increased susceptibility to osteoporosis, with shared underlying mechanisms. This study aimed to investigate the association between vascular function and bone mineral density (BMD). METHODS: We conducted a cross-sectional study of 49 patients with RA at Tan Tock Seng Hospital, Singapore. Endothelial function was measured as reactive hyperaemia index (RHI)-endothelial peripheral arterial tonometry and aortic stiffness as carotid-femoral pulse wave velocity (cf-PWV) using SphygmoCor. Univariable and multivariable linear regression analyses were performed to evaluate the associations between BMD and vascular function. We used natural logarithm RHI (lnRHI) and cf-PWV as response variables, and each BMD as covariate, adjusting for body mass index, positive anti-cyclic citrullinated peptide, cumulative prednisolone dose, hydroxychloroquine use and Systematic COronary Risk Evaluation 2. RESULTS: We recruited 49 patients (mean age 61.08 ± 8.20 years), of whom 44 (89.80%) were women and 39 (81.25%) were Chinese. Significant associations were found between lnRHI and BMD at the lumbar spine (β = 0.4289, P = 0.037) and total hip (β = 0.7544, P = 0.014) in univariable analyses. Multivariable analyses confirmed these associations, showing that lower BMD at the lumbar spine (β = 0.7303, P = 0.001), femoral neck (β = 0.8694, P = 0.030) and total hip (β = 0.8909, P = 0.010) were significantly associated with worse lnRHI. No significant associations were found between BMD and cf-PWV. CONCLUSION Lower BMD is associated with endothelial dysfunction, but not aortic stiffness in patients with RA. Further longitudinal studies are needed to confirm these associations and understand the underlying mechanisms.
Humans ; Arthritis, Rheumatoid/complications* ; Female ; Male ; Bone Density ; Middle Aged ; Cross-Sectional Studies ; Vascular Stiffness ; Aged ; Singapore ; Pulse Wave Analysis ; Osteoporosis/complications* ; Endothelium, Vascular/physiopathology* ; Cardiovascular Diseases/complications* ; Carotid-Femoral Pulse Wave Velocity ; Hyperemia

INTRODUCTION: Hydroxychloroquine (HCQ), originally an antimalarial drug, is currently used to treat multiple disorders, especially rheumatic diseases. Given its good efficacy and safety, HCQ is widely administered in pregnant patients. However, the safety profile of HCQ during pregnancy remains controversial due to limited research. In addition, HCQ has been reported to reduce preeclampsia in patients with systemic lupus erythematosus (SLE) and could potentially alleviate the symptom of preeclampsia. However, the clinical profile and molecular mechanism of HCQ in preeclampsia is yet to be fully understood. METHOD: We reviewed the literature on HCQ treatment in pregnancy with rheumatic diseases and preeclamp-sia in PubMed and Web of Science. We also discussed the safety of long-term therapy with HCQ during pregnancy. RESULTS: HCQ mainly modulates autoimmune response through inhibition of lysosomal function, toll-like receptor (TLR) signalling, nicotinamide adenine dinucleotide phosphate-mediated oxidative stress and autophagy. Benefits of HCQ in treating rheumatic diseases, including antiphospholipid syndrome, rheumatoid arthritis and Sjogren's syndrome during pregnancy, has been demonstrated in clinics. In particular, multiple clinical guidelines recommend HCQ as an indispensable therapeutic drug for pregnant patients with SLE. Additionally, it may potentially function in preeclampsia to improve clinical symptoms. CONCLUSION HCQ is effectively used for rheumatic diseases during pregnancy. The benefits of HCQ treatment in rheumatic diseases outweigh the risk of adverse reactions it induces in pregnant women.
Humans ; Hydroxychloroquine/pharmacology* ; Pregnancy ; Female ; Antirheumatic Agents/pharmacology* ; Rheumatic Diseases/drug therapy* ; Pregnancy Complications/drug therapy* ; Pre-Eclampsia/prevention & control* ; Lupus Erythematosus, Systemic/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Antiphospholipid Syndrome/drug therapy* ; Sjogren's Syndrome/drug therapy*

OBJECTIVE: To explore the surgical technique and clinical outcomes of biological total hip arthroplasty(THA) combined with impacting bone grafting for the treatment of moderate to severe acetabular invagination secondary to rheumatoid arthritis(RA). METHODS: Total of 20 patients(28 hips) with RA secondary to acetabular invagination were treated with THA of bioprosthesis combined with autogenous bone grafting from January 2012 to October 2020, including 5 males(8 hips) and 15 females(20 hips) with an average age of (55.10±4.96) years old from 45 to 64 years old. The depth of acetabular invagination was 8.43 to 16.25 mm with an average of (11.91±2.59) mm. According to Sotello-Garza and Charnley classification criterion, there were 15 cases(23 hips) of type Ⅱ(protrusio acetabuli 6 to 15 mm), and 5 cases(5 hips) of type Ⅲ(protrusio acetabuli>15 mm). Autologous femoral head granular bone and(or) allograft impacting grafting were used to reconstruct the acetabum, the biological porous acetabular cup was fixed by pressure fitting. At the postoperative follow-up, the activity function of the hip joint, the length of both lower limbs, VAS and Harris score were evaluated, and the healing of bone graft, the restoration of the hip rotation center and loosening of prosthesis were assessed by X-ray. RESULTS: The operation time was 75 to 160 min with anverage of (103.32±18.18) min, the intraoperative blood loss was 150 to 650 ml with an average of (319.64±122.61) ml. There were no neurovascular complications during the operation. All patients were followed up from 2 to 10 years with an average of (5.45±2.50) years. The horizontal distance between the center of femoral head and the Kohler's line was increased from (11.40±1.85) mm preoperatively to (25.99±2.56) mm at the final follow-up(P<0.01), and the vertical distance between the center of femoral head and the line joining bilateral ischial tuberosities was decreased from (89.36±5.20) mm preoperatively to (71.84±3.55) mm at the final follow-up(P<0.01). The range of flexion motion of hip joint increased from (44.43±10.57)° preoperatively to (98.75±12.52)° at the final follow-up(P<0.01), the range of abduction motion of hip joint increased from (12.50 ±6.01)°preoperatively to final follow-up (32.82±5.39)°(P<0.01). The discrepancy of both lower limbs was significantly decreased from (19.39±5.93) mm preoperatively to (6.64±2.87) mm at the final follow-up(P<0.01). The VAS decreased from (5.36±0.78) preoperatively to (1.82±0.86) at the final follow-up(P<0.05), and the Harris score increased from (41.39±7.77) preoperatively to (89.00±4.67) at the final follow-up(P<0.01). All the patients could move independently without assistance. Among them, 2 patients(2 hips) had hip pain after exercise, and 1 patient(1 hip) suffered from periprosthetic fracture due to fall. CONCLUSION Autologous femoral head granular bone grafting can reconstruct the acetabulum, and restore the rotation center of the hip joint, combined with biological porous tantalum/titanium acetabular cup can achieve good short-and medium-term outcomes in the treatment of moderate to severe acetabular invagination secondary to rheumatoid arthritis.
Humans ; Female ; Male ; Middle Aged ; Arthroplasty, Replacement, Hip/methods* ; Bone Transplantation/methods* ; Arthritis, Rheumatoid/complications* ; Acetabulum/surgery*

The lungs are one of the most common extra-articular organs involved in rheumatoid arthritis (RA), which is reported to occur in up to 60% to 80% of RA patients. Respiratory complications are the second leading cause of death due to RA. Although there is a wide spectrum of RA-associated respiratory diseases, interstitial lung disease is the most common manifestation and it impacts the prognosis of RA. There has been progress in understanding the management and progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and RA-associated respiratory diseases recently, for example, opportunistic pulmonary infectious diseases and toxicity from RA therapies. From a chest physicians' perspective, we will update the diagnosis and treatment of RA-associated ILD, methotrexate-associated lung disease, and the complication of Pneumocystis jiroveci pneumonia in RA in this review.
Humans ; Arthritis, Rheumatoid/complications* ; Methotrexate/therapeutic use* ; Lung Diseases, Interstitial/complications* ; Prognosis ; Lung

OBJECTIVE: To study the correlation between dyslipidemia and rheumatoid arthritis associa-ted interstitial lung disease (RA-ILD) by retrospective analysis of the clinical data. METHODS: The clinical data of patients with rheumatoid arthritis (RA), who were hospitalized in the Department of Rheumatism and Immunology of Peking University Shenzhen Hospital from January 2015 to July 2020 and fulfilled the criteria of the 2010 Rheumatoid Arthritis Classification Criteria established by American College of Rheumatology/European League Against Rheumatism collaborative initiative, were collected and analyzed. RESULTS: There were 737 RA patients included, of whom 282(38.26%)were with interstitial lung disease (ILD). The median time from the onset of the first RA-related clinical symptoms to the onset of ILD was 13 years (95%CI 11.33-14.67). By multivariate Logistic regression analysis, we found that low-density lipoprotein cholesterol (LDL-C) was an independent risk factor for RA-ILD (OR 1.452, 95%CI 1.099-1.918, P=0.009), whereas high-density lipoprotein cholesterol (HDL-C) was a protective factor for RA-ILD (OR 0.056, 95%CI 0.025-0.125, P < 0.001). The RA patients with high LDL-C or low HDL-C had higher incidence of ILD than that of the RA patients with normal LDL-C or HDL-C(57.45% vs. 36.96%, P < 0.001; 47.33% vs. 33.81%, P < 0.001, respectively). The median time of ILD onset in the RA patients with low HDL-C was shorter than that of the RA patients with normal HDL-C [10.0(95%CI 9.33-10.67)years vs.17.0 (95%CI 14.58-19.42) years, P < 0.001]. HDL-C level was negatively correlated with disease activity. Among the RA-ILD patients, the patients with low HDL-C had higher percentage of usual interstitial pneumonia (UIP) then that of the patients with normal HDL-C (60.00% vs. 53.29%, P=0.002). The RA-ILD patients with high LDL-C had higher incidence rate of decrease in forced vital capacity (FVC) than that of the RA-ILD patients with normal LDL-C (50.00% vs. 21.52%, P=0.015). The RA-ILD patients with low HDL-C had higher incidence rate of decrease in FVC (26.92% vs. 16.18%, P=0.003) and carbon monoxide diffusion (80.76% vs. 50.00%, P=0.010) than that of RA-ILD patients with normal HDL-C. CONCLUSION LDL-C was possibly a potential independent risk factor for RA-ILD. HDL-C was possibly a potential protective factor for RA-ILD. HDL-C level was negatively correlated with disease activity of RA. The median time of ILD onset in the RA patients with low HDL-C was significantly shorter than that of the RA patients with normal HDL-C.
Humans ; Retrospective Studies ; Cholesterol, LDL ; Arthritis, Rheumatoid/complications* ; Lung Diseases, Interstitial/complications* ; Dyslipidemias/epidemiology*

OBJECTIVE: To analyze the clinical features of overweight and obese rheumatoid arthritis (RA)patients, and the relationship between body mass index (BMI) and disease characteristics. METHODS: The demographic data, extra-articular manifestations, comorbidities, and disease activity of RA patients admitted to the Rheumatology and Immunology Department of Peking University Third Hospital from January 2015 to December 2020 were collected, and the above characteristics of overweight and obese RA patients were retrospectively analyzed. According to the WHO, BMI≥30 kg/m² referred to obese individuals, 25≤BMI < 30 kg/m² referred to overweight individuals, 18.5≤BMI < 25 kg/m² referred to normal individuals, BMI < 18.5 kg/m² referred to reduced body mass individuals. t test was used for the quantitative data in accordance with normal distribution. Wilcoxon rank sum test was used for the quantitative data of non-normal distribution. The qualitative data were analyzed by chi square test. But while 1≤theoretical frequency < 5, Chi square test of corrected four grid table was used. And Fisher exact probability method was used when theoretical frequency < 1. Analyzing whether overweight or obesity was associated with comorbidities using Logistic regression adjusted confounding factors. RESULTS: A total of 481 RA patients were included in this study, with an average BMI value of (23.28±3.75) kg/m².Of the patients, 31 cases (6.5%) were with BMI < 18.5 kg/m², 309 cases (64.2%) with 18.5≤ BMI < 25 kg/m², amounting to 340 cases (70.7%). There were 119 overweight individuals (25≤ BMI < 30 kg/m², 24.7%) and 22 obese individuals (BMI≥30 kg/m², 4.6%), totaling 141 (29.3%).The proportion of the overweight and obese RA patients suffering from hypertension (57.4% vs. 39.1%, P < 0.001), diabetes (25.5% vs. 15.0%, P=0.006), hyperlipidemia (22.7% vs. 10.9%, P=0.001), fatty liver (28.4% vs. 7.4%, P < 0.001), osteoarthritis (39.0% vs. 29.4%, P=0.040) was significantly higher, and the proportion of the patients with osteoporosis(59.6% vs. 70.9%, P=0.016) and anemia (36.2% vs. 55.6%, P < 0.001) was significantly lower. However, there was no difference between the two groups in coronary heart disease (5.7% vs. 7.6%, P=0.442), cerebrovascular disease (6.4% vs. 8.8%, P=0.372) and peripheral atherosclerosis (9.2% vs. 7.6%, P=0.565).The median C-reactive protein (CRP, 1.52 mg/dL vs. 2.35 mg/dL, P=0.008), median erythrocyte sedimentation rate (ESR, 34.0 mm/h vs. 50.0 mm/h, P=0.003), pain visual simulation score (VAS) (3.66±3.08 vs. 4.40±2.85, P=0.011), and 28 joint disease activity scores (DAS-28, 5.05±1.60 vs. 5.45±1.52, P=0.010) in the overweight and obese RA group were all lower than those in the normal and reduced weight groups. Multivariate regression analysis showed that overweight and obesity was an independent risk factor for hypertension, diabetes, hyperlipidemia and fatty liver, and had protective effects on osteoporosis and anemia. CONCLUSION In RA patients, RA disease activity is lower in overweight and obesity patients. Overweight and obesity is associated with hypertension, diabetes and hyperlipidemia, but not with cardiovascular and cerebrovascular diseases.
Humans ; Body Mass Index ; Overweight/epidemiology* ; Retrospective Studies ; Arthritis, Rheumatoid/epidemiology* ; Obesity/epidemiology* ; Diabetes Mellitus ; Hypertension/complications* ; Fatty Liver/complications* ; Hyperlipidemias/complications* ; Osteoporosis/complications* ; Anemia