Fibroblast-Like Synoviocytes Glucose Metabolism as a Therapeutic Target in Rheumatoid Arthritis.

Metabolomic studies show that rheumatoid arthritis (RA) is associated with metabolic disruption that may be therapeutically targetable. Among them, glucose metabolism and glycolytic intermediaries seem to have an important role in fibroblast-like synoviocytes (FLS) phenotype and might contribute to early stage disease pathogenesis. RA FLS are transformed from quiescent to aggressive and metabolically active cells and several works have shown that glucose metabolism is increased in activated FLS. Glycolytic inhibitors reduce not only FLS aggressive phenotype in vitro but also decrease bone and cartilage damage in several murine models of arthritis. Essential glycolytic enzymes, including hexokinase 2 (HK2) and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB) enzymes, have important roles in FLS behavior. Of interest, HK2 is an inducible enzyme present only in the inflamed rheumatic tissues compared to osteoarthritis synovium. It is a contributor to glucose metabolism that could be selectively targeted without compromising systemic homeostasis as a novel approach for combination therapy independent of systemic immunosuppression. More information about metabolic targets that do not compromise global glucose metabolism in normal cells is needed

Practical screening tools for sarcopenia in patients with systemic sclerosis

Introduction In view of the method of diagnosing sarcopenia being complex and considered to be difficult to introduce into routine practice, the European Working Group on Sarcopenia in Older People (EWGSOP) recommends the use of the SARC-F questionnaire as a way to introduce assessment and treatment of sarcopenia into clinical practice. Only recently, some studies have turned their attention to the presence of sarcopenia in systemic sclerosis (SSc).There is no data about performance of SARC-F and other screening tests for sarcopenia in this population. Objective To compare the accuracy of SARC-F, SARC-CalF, SARC-F+EBM, and Ishii test as screening tools for sarcopenia in patients with SSc. Methods Cross-sectional study of 94 patients with SSc assessed by clinical and physical evaluation. Sarcopenia was defined according to the revised 2019 EWGSOP diagnostic criteria (EWGSOP2) with assessments of dual-energy X-ray absorptiometry, handgrip strength, and short physical performance battery (SPPB). As case finding tools, SARC-F, SARC-CalF, SARC-F+EBM and Ishii test were applied, including data on calf circumference, body mass index, limitations in strength, walking ability, rising from a chair, stair climbing, and self reported number of falls in the last year. The screening tests were evaluated through receiver operating characteristic (ROC) curves. Standard measures of diagnostic accuracy were computed using the EWGSOP2 criteria as the gold standard for diagnosis of sarcopenia. Results Sarcopenia was identified in 15 (15.9%) patients with SSc by the EWGSOP2 criteria. Area under the ROC curve of SARC-F screening for sarcopenia was 0.588 (95% confidence interval (CI) 0.420–0.756, p = 0.283). The results of sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR) and diagnostic Odds Ratio (DOR) with the EWGSOP2 criteria as the gold standard were 40.0% (95% CI, 19.8–64.2), 81.0% (95% CI, 71.0–88.1), 2.11 (95% CI, 0.98–4.55), 0.74 (95% CI, 0.48–1.13) and 2.84 (95% CI, 0.88–9.22), respectively. SARC-CalF and SARC-F+EBM showed better sensitivity (53.3%, 95% CI 30.1–75.2 and 60.0%, 95% CI 35.7–80.2, respectively) and specificity (84.8%, 95% CI 75.3–91.1 and 86.1%, 95% CI 76.8–92.0, respectively) compared with SARC-F. The best sensitivity was obtained with the Ishii test (86.7%, 95% CI 62.1–96.3), at the expense of a small loss of specificity (73.4%, 95% CI 62.7–81.9). Comparing the ROC curves, SARC-F performed worse than SARC-CalF, SARC-F+EBM and Ishii test as a sarcopenia screening tool in this population (AUCs 0.588 vs. 0.718, 0.832, and 0.862, respectively). Direct comparisons between tests revealed differences only between SARC-F and Ishii test for sensitivity (p = 0.013) and AUC (p = 0.031). Conclusion SARC-CalF, SARC-F+EBM, and Ishii test performed better than SARC-F alone as screening tools for sarcopenia in patients with SSc. Considering diagnostic accuracy and feasibility aspects, SARC-F+EBM seems to be the most suitable screening tool to be adopted in routine care of patients with SSc