Development of Rheumatoid Arthritis: Preclinical Biomarkers and Prediction

Dijkmans, B.A.C. [Promotor]Aarden, L.A. [Promotor]Schaardenburg, D. van [Copromotor

Subluxation of the first carpometacarpal joint and age are important factors in reduced hand strength in patients with hand osteoarthritis

Objective: To investigate the determinants of hand strength in patients with hand osteoarthritis (OA). Method: Pinch and cylinder grip strength were measured in 527 patients with hand OA diagnosed by their treating rheumatologist from the Hand OSTeoArthritis in Secondary care (HOSTAS) study. Radiographs of hands (22 joints) were scored 0-3 (scaphotrapeziotrapezoid and first interphalangeal joints 0-1) on osteophytes and joint space narrowing following the Osteoarthritis Research Society International atlas. The first carpometacarpal joint (CMC1) was scored 0-1 for subluxation. Pain was assessed with the Australian/Canadian Hand Osteoarthritis Index pain subscale, and health-related quality of life with the Short Form-36. Regression analysis served to investigate associations of hand strength with patient, disease, and radiographic features. Results: Hand strength was negatively associated with female sex, age, and pain. Reduced hand strength was associated with reduced quality of life, although less after adjusting for pain. Radiographic features of hand OA were associated with reduced grip strength when solely adjusted for sex and body mass index, but only CMC1 subluxation in the dominant hand remained significantly associated with pinch grip adjusted additionally for age (-0.511 kg, 95% confidence interval -0.975; -0.046). Mediation analysis showed low and not significant percentages of mediation of hand OA in the association between age and grip strength. Conclusions: Subluxation of CMC1 is associated with reduced grip strength, whereas associations with other radiographic features seem to be confounded by age. In the relationship between age and hand strength, radiographic hand OA severity is not an important mediator.Pathophysiology and treatment of rheumatic disease

The association of clinical and structural knee osteoarthritis with physical activity in the middle-aged population: the NEO study

Objective: To investigate if knee osteoarthritis (OA) is associated with lower physical activity in the general middle-aged Dutch population, and if physical activity is associated with patient-reported outcomes in knee OA. Design: Clinical knee OA was defined in the Netherlands Epidemiology of Obesity population using the ACR criteria, and structural knee OA on MRI. We assessed knee pain and function with the Knee Injury and Osteoarthritis Score (KOOS), health-related quality of life (HRQoL) with the Short Form-36, and physical activity (in Metabolic Equivalent of Task (MET) hours) with the Short Questionnaire to Assess Health-enhancing physical activity. We analysed the associations of knee OA with physical activity, and of physical activity with knee pain, function, and HRQoL in knee OA with linear regression adjusted for potential confounders. Results: Clinical knee OA was present in 14% of 6,212 participants, (mean age 56 years, mean BMI 27 kg/m(2), 55% women, 24% having any comorbidity) and structural knee OA in 12%. Clinical knee OA was associated with 9.60 (95% CI 3.70; 15.50) MET hours per week more physical activity, vs no clinical knee OA. Structural knee OA was associated with 3.97 (-7.82; 15.76) MET hours per week more physical activity, vs no structural knee OA. In clinical knee OA, physical activity was not associated with knee pain, function or HRQoL. Conclusions: Knee OA was not associated with lower physical activity, and in knee OA physical activity was not associated with patient-reported outcomes. Future research should indicate the optimal treatment advice regarding physical activity for individual knee OA patients. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Cardiovascular Aspects of Radiolog

Identifying advanced stage NSCLC patients who benefit from afatinib therapy using 18F-afatinib PET/CT imaging

Objectives: Non-small cell lung cancer (NSCLC) tumors harboring common (exon19del, L858R) and uncommon (e.g. G719X, L861Q) activating epidermal growth factor receptor (EGFR) mutations are best treated with EGFR tyrosine kinase inhibitors (TKI) such as the first-generation EGFR TKI erlotinib, second-generation afatinib or third-generation osimertinib. However, identifying these patients through biopsy is not always possible. Therefore, our aim was to evaluate whether 18F-afatinib PET/CT could identify patients with common and uncommon EGFR mutations. Furthermore, we evaluated the relation between tumor 18F-afatinib uptake and response to afatinib therapy.Materials and methods: 18F-afatinib PET/CT was performed in 12 patients: 6 EGFR wild type (WT), 3 EGFR common and 3 EGFR uncommon mutations. Tumor uptake of 18F-afatinib was quantified using TBR_WB60-90 (tumor-to-whole blood activity ratio 60-90 min post-injection) for each tumor. Response was quantified per lesion using percentage of change (PC): [(response measurement (RM)?baseline measurement (BM))/BM]?100. Statistical analyses were performed using t-tests, correlation plots and sensitivity/specificity analysis.Results: Twenty-one tumors were identified. Injected dose was 348 ? 31 MBq. Group differences were significant between WT versus EGFR (common and uncommon) activating mutations (p = 0.03). There was no significant difference between EGFR common versus uncommon mutations (p = 0.94). A TBR_WB60-90 cut-off value of 6 showed the best relationship with response with a sensitivity of 70 %, a specificity of 100 % and a positive predictive value of 100 %.Conclusion: 18F-afatinib uptake was higher in tumors with EGFR mutations (common and uncommon) compared to WT. Furthermore, a TBR_WB60-90 cut-off of 6 was found to best predict response to therapy. 18F-afatinib PET/ CT could provide a means to identify EGFR mutation positive patients who benefit from afatinib therapy.Pathogenesis and treatment of chronic pulmonary disease

Measures of Hand Function

Pathophysiology and treatment of rheumatic disease

The management of hand osteoarthritis: The rheumatologist's perspective

Hand osteoarthritis (OA) is treated by several medical professionals. In this review the rheumatologist's perspective will be conveyed. The rheumatologist tasks are to diagnose hand OA, exclude other causes of patient's complaints, and provide treatment. The rheumatologist therefore has a distinctive and important role in hand OA treatment. Although no disease modifying treatment exists, there are multiple options for managing hand OA in rheumatology practice, with the goal of achieving symptom relief and optimizing hand function. These treatments can be non-pharmacological or pharmacological. In this review we will provide a summary of evidence-based management options based on existing guidelines. Furthermore, we will describe common practice among rheumatologists for hand OA management. In order to do so, we performed a literature review of studies addressing treatment modality usage for hand OA. The review comprised 25 studies, which were heterogeneous in terms of treatment modality usage. In addition, a detailed description of care usage by patients in a Rheumatology outpatient clinic is given, based on data of our Hand OSTeoArthritis in Secondary care primary hand OA cohort. The large majority of these patients used any form of hand OA treatment (83%). Non-pharmacological treatment was less frequently used (47%) than pharmacological treatment (77%).(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/