Association between Several Clinical and Radiological Determinants with Long-Term Clinical Progression and Good Prognosis of Lower Limb Osteoarthritis

OBJECTIVE: To investigate the factors associated with clinical progression and good prognosis in patients with lower limb osteoarthritis (OA). METHODS: Cohort study of 145 patients with OA in either knee, hip or both. Progression was defined as 1) new joint prosthesis or 2) increase in WOMAC pain or function score during 6-years follow-up above pre-defined thresholds. Patients without progression with decrease in WOMAC pain or function score lower than pre-defined thresholds were categorized as good prognosis. Relative risks (RRs) for progression and good prognosis with 95% confidence interval (95% CI) were calculated by comparing the highest tertile or category to the lowest tertile, for baseline determinants (age, sex, BMI, WOMAC pain and function scores, pain on physical examination, total range of motion (tROM), osteophytes and joint space narrowing (JSN) scores), and for worsening in WOMAC pain and function score in 1-year. Adjustments were performed for age, sex, and BMI. RESULTS: Follow-up was completed by 117 patients (81%, median age 60 years, 84% female); 62 (53%) and 31 patients (26%) showed progression and good prognosis, respectively. These following determinants were associated with progression: pain on physical examination (RR 1.2 (1.0 to 1.5)); tROM (1.4 (1.1 to 1.6); worsening in WOMAC pain (1.9 (1.2 to 2.3)); worsening in WOMAC function (2.4 (1.7 to 2.6)); osteophytes 1.5 (1.0 to 1.8); and JSN scores (2.3 (1.5 to 2.7)). Worsening in WOMAC pain (0.1 (0.1 to 0.8)) and function score (0.1 (0.1 to 0.7)), were negatively associated with good prognosis. CONCLUSION: Worsening of self-reported pain and function in one year, limited tROM and higher osteophytes and JSN scores were associated with clinical progression. Worsening in WOMAC pain and function score in 1- year were associated with lower risk to have good prognosis. These findings help to inform patients with regard to their OA prognosis

Body mass index and extent of MRI-detected inflammation: opposite effects in rheumatoid arthritis versus other arthritides and asymptomatic persons

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Body mass index and treatment survival in patients with RA starting treatment with TNFalpha-inhibitors: long-term follow-up in the real-life METEOR registry

OBJECTIVES: To study whether there is an association between body mass index (BMI) category and survival of various tumour necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA) patients in a real-life longitudinal international registry. METHODS: Data from 5230 patients with RA starting treatment with any TNFi were selected from the METEOR registry. Patients were divided into six BMI categories: 3.7% underweight, BMI \u3c 18.5 kg/m(2); 46% normal weight, BMI 18.5-25 kg/m(2); 32% pre-obesity, BMI 25-30 kg/m(2); 13% obesity class I, BMI 30-35 kg/m(2); 3.4% obesity class II, BMI 35-40 kg/m(2); and 1.6% obesity class III, BMI \u3e 40 kg/m(2). Time on treatment in the different BMI categories was compared for all TNFi combined and for the infliximab, adalimumab and etanercept separately, using Kaplan-Meier curves and Cox regression analyses. Cox regression analyses were adjusted for potential confounders, with follow-up censored at 5000 days. RESULTS: Patients in obesity class II (HR 1.28, 95% CI 1.06 to 1.54) and III (HR 1.67, 95% CI 1.29 to 2.18) and underweight patients (HR 1.30, 95% CI 1.07 to 1.58) showed statistically significantly shorter TNFi survival than normal weight patients. The effect in underweight patients was strongest for infliximab (HR 1.82, 95% CI 1.20 to 2.76), the effect in overweight patients was strongest for infliximab (category II (HR 1.49, 95% CI 0.98 to 2.26); category III (HR 1.46, 95% CI 0.79 to 2.71)) and etanercept (category II (HR 1.27 95% CI 0.98 to 1.65); category III (HR 1.79, 95% CI 1.25 to 2.55)). No significant effect modification from reported pain was found. CONCLUSION: Both underweight and overweight patients discontinued TNFi treatment earlier than normal weight patients, without evidence of reported pain as the main determinant. It remains uncertain what determines TNFi survival in individual patients

The fine specificity of IgM anti-citrullinated protein antibodies (ACPA) is different from that of IgG ACPA

Pathophysiology and treatment of rheumatic disease

Autoimmune Responses in the Rheumatoid Synovium

Rene Toes and Tom Huizinga discuss a new study indicating that lymphoneogenesis in the inflamed synovial tissue of patients with rheumatoid arthritis is fostering potentially pathogenic immune responses

Association of the 6q23 region with the rate of joint destruction in rheumatoid arthritis

BACKGROUND: /st> Two novel genetic polymorphisms on chromosome 6q23 are associated with susceptibility to rheumatoid arthritis (RA). Both polymorphisms (rs6920220 and rs10499194) reside in a region close to the gene encoding tumour necrosis factor alpha-induced protein 3 (TNFAIP3). TNFAIP3 is a negative regulator of NF-kappaB and is involved in inhibiting TNF-receptor-mediated signalling effects. Interestingly, the initial associations were detected in patients with longstanding RA. However, no association was found for rs10499194 in a Swedish cohort with early arthritis. This might be caused by over-representation of patients with severe disease in cohorts with longstanding RA. OBJECTIVE: /st> To analyse the effect of the 6q23 region on the rate of joint destruction. METHODS: /st> Five single nucleotide polymorphisms in 6q23 were genotyped in 324 Dutch patients with early RA. Genotypes were correlated with progression of radiographic joint damage for a follow-up time of 5 years. RESULTS: /st> Two polymorphisms (rs675520 and rs9376293) were associated with severity of radiographic joint damage in patients positive for anti-citrullinated protein/peptide antibodies (ACPA). Importantly, the effects were present after correction for confounding factors such as secular trends in treatment. CONCLUSIONS: /st> These data associate the 6q23 region with the rate of joint destruction in ACPA+ RA.Pathophysiology and treatment of rheumatic disease

Selective Involvement of the Amygdala in Systemic Lupus Erythematosus

BACKGROUND: Antibodies specifically affect the amygdala in a mouse model of systemic lupus erythematosus (SLE). The aim of our study was to investigate whether there is also specific involvement of the amygdala in human SLE. METHODS AND FINDINGS: We analyzed a group of 37 patients with neuropsychiatric SLE (NP-SLE), 21 patients with SLE, and a group of 12 healthy control participants with diffusion weighted imaging (DWI). In addition, in a subset of eight patients, plasma was available to determine their anti-NMDAR antibody status. From the structural magnetic resonance imaging data, the amygdala and the hippocampus were segmented, as well as the white and gray matter, and the apparent diffusion coefficient (ADC) was retrieved. ADC values between controls, patients with SLE, and patients with NP-SLE were tested using analysis of variance with post-hoc Bonferroni correction. No differences were found in the gray or white matter segments. The average ADC in the amygdala of patients with NP-SLE and SLE (940 × 10(−6) mm(2)/s; p = 0.006 and 949 × 10(−6) mm(2)/s; p = 0.019, respectively) was lower than in healthy control participants (1152 × 10(−6) mm(2)/s). Mann-Whitney analysis revealed that the average ADC in the amygdala of patients with anti-NMDAR antibodies (n = 4; 802 × 10(−6) mm(2)/s) was lower (p = 0.029) than the average ADC of patients without anti-NMDAR antibodies (n = 4; 979 × 10(−6) mm(2)/s) and also lower (p = 0.001) than in healthy control participants. CONCLUSIONS: This is the first study to our knowledge to observe damage in the amygdala in patients with SLE. Patients with SLE with anti-NMDAR antibodies had more severe damage in the amygdala compared to SLE patients without anti-NMDAR antibodies

MRI-Based classification of neuropsychiatric systemic lupus erythematosus patients with self-supervised contrastive learning

Introduction/Purpose: Systemic lupus erythematosus (SLE) is a chronic auto-immune disease with a broad spectrum of clinical presentations, including heterogeneous neuropsychiatric (NP) syndromes. Structural brain abnormalities are commonly found in SLE and NPSLE, but their role in diagnosis is limited, and their usefulness in distinguishing between NPSLE patients and patients in which the NP symptoms are not primarily attributed to SLE (non-NPSLE) is non-existent. Self-supervised contrastive learning algorithms proved to be useful in classification tasks in rare diseases with limited number of datasets. Our aim was to apply self-supervised contrastive learning on T1-weighted images acquired from a well-defined cohort of SLE patients, aiming to distinguish between NPSLE and non-NPSLE patients. Subjects and Methods: We used 3T MRI T1-weighted images of 163 patients. The training set comprised 68 non-NPSLE and 34 NPSLE patients. We applied random geometric transformations between iterations to augment our data sets. The ML pipeline consisted of convolutional base encoder and linear projector. To test the classification task, the projector was removed and one linear layer was measured. Validation of the method consisted of 6 repeated random sub-samplings, each using a random selection of a small group of patients of both subtypes. Results: In the 6 trials, between 79% and 83% of the patients were correctly classified as NPSLE or non-NPSLE. For a qualitative evaluation of spatial distribution of the common features found in both groups, Gradient-weighted Class Activation Maps (Grad-CAM) were examined. Thresholded Grad-CAM maps show areas of common features identified for the NPSLE cohort, while no such communality was found for the non-NPSLE group. Discussion/Conclusion: The self-supervised contrastive learning model was effective in capturing common brain MRI features from a limited but well-defined cohort of SLE patients with NP symptoms. The interpretation of the Grad-CAM results is not straightforward, but indicates involvement of the lateral and third ventricles, periventricular white matter and basal cisterns. We believe that the common features found in the NPSLE population in this study indicate a combination of tissue loss, local atrophy and to some extent that of periventricular white matter lesions, which are commonly found in NPSLE patients and appear hypointense on T1-weighted images