Rabbit Anti-Human BRAF (Phospho-Thr753) polyclonal antibody

Introduction The objective was to evaluate the relationships between multimorbidity and overall fatigue as well as fatigue subdomains in patients with rheumatoid arthritis (RA). Methods A cross-sectional study of a population-based cohort of patients with RA was performed. Fatigue was assessed using the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ). Patients' medical records were reviewed for 25 chronic comorbidities prior to the BRAF-MDQ. Linear and logistic regression models were used to estimate the differences in BRAF-MDQ total and subdomain (physical, living, cognitive, and emotional) scores associated with multimorbidity, adjusting for age, sex, disease duration, obesity, smoking, C-reactive protein, and RA autoantibodies. Higher BRAF-MDQ scores indicate greater fatigue severity. Results The cohort included 192 patients, median age 62 years, and median RA duration 13 years. Multimorbidity was common with 93 (48%) having >= 2 comorbidities, and 27 (14%) having >= 4 comorbidities. The median BRAF-MDQ total score was 9 (interquartile range 3-18), with higher scores indicating greater fatigue. Patients with >= 4 comorbidities had higher total BRAF-MDQ scores (median 16.5, interquartile range: 6.8-24.8) than patients with < 4 comorbidities (7.5, 2.8-16.0; p = 0.014). Each additional comorbidity was associated with a 2.33 (95% confidence interval [CI] 1.10-3.56) unit increase in total BRAF-MDQ score (p < 0.001), and the presence of >= 4 comorbidities was associated with a 9.33 (95% CI 3.92-14.7) unit increase in total BRAF-MDQ score. Multimorbidity was significantly associated with all four fatigue subdomains in adjusted models. Conclusions Multimorbidity is associated with increased fatigue in patients with RA. The findings suggest that interventions targeting multimorbidity could help alleviate treatment-refractory fatigue in patients with RA and other rheumatic diseases.

Aims Recently, a novel isoform of anaplastic lymphoma kinase, with alternative transcription initiation (ALK(ATI)), has been described in melanoma and is susceptible to targeted ALK-inhibitor therapy. Clinical outcomes of patients with ALK(ATI)mutated melanoma as well as correlation with immunohistochemical (IHC) methods have not yet been described. Methods and results Clinicopathological characteristics were abstracted for 324 patients with metastatic melanoma (MM). IHC, fluorescencein-situhybridisation and RNA-based digital molecular analysis assays were performed on archival tissue from 173 stage III and 192 stage IV tumours. ALK(ATI)was identified in 12.7 and 4.8% stage III and IV tumours, respectively. Discrete presentations of the ALK(ATI)are seen: isolated ALK(ATI)(n = 20) and mixed ALK(ATI)(combined ALK(ATI)and ALK(WT);n = 7). Isolated ALK(WT)expression (n = 4) was seen with no ALK fusions. Stage III patients showed improved survival with ALK(ATI)expression compared to those with ALK(WT)or no expression [5-year survival 80, 95% confidence interval (CI) = 57-100% versus 43%, 95% CI = 34-55%,P = 0.013]. Clinicopathological characteristics were not statistically significant. Strong diffuse cytoplasmic staining of ALK IHC (n = 12) has a sensitivity of 52.2%, specificity 100%, PPV of 100% and NPV of 92.5% of detecting isolated ALK(ATI). Conclusion Presence of ALK(ATI)is a good prognostic indicator in MM. ALK IHC and digital molecular analysis can be incorporated into MM evaluation to identify patients with ALK(ATI)for targeted therapy.