Evaluation of subclinical retinopathy and angiopathy with OCT and OCTA in patients with systemic lupus erythematosus.

PURPOSE: To evaluate the choroidal and retinal layers with optical coherence tomography (OCT) and retinal microvascular structures with optical coherence tomography angiography (OCTA) in systemic lupus erythematosus (SLE) patients. METHOD: In this prospective, cross-sectional and comparative study, a total of 35 SLE patients and 35 healthy control participants were included. SLE patients who were using hydroxychloroquine (HCQ) and/or immunosuppressive agents are evaluated with OCT and OCTA. SLE patients who have no HCQ maculopathy observed in OCT were included in the patient group. RESULTS: Mean macular thickness and ganglion cell inner plexiform layer (GC-IPL) thicknesses were thinner in the patient group. When the parameters obtained with OCTA were evaluated, vessel (VD) and perfusion density (PD) were significantly lower in the patient group. Central foveal thickness and foveal avascular zone parameters were negatively correlated. In addition, VD and PD, and GC-IPL thicknesses were positively correlated. CONCLUSION: Application of OCTA for the evaluation of microvasculature in SLE patients may be useful in subclinical changes.

Retinal and choroidal vascular structures are affected in axial spondyloarthritis: an optical coherence tomography study.

PURPOSE: The aim of this study is to evaluate the retinal and choroidal structures in r- and nr-axSpA patients using spectral domain optical coherence tomography (SD-OCT) and to compare changes with healthy controls. METHODS: In this cross-sectional study, 70 axSpA patients (50 radiographic- and 20 nr-axSpA) and 50 healthy control subjects were included. Choroidal thickness (ChT), macular thickness, retinal nerve fiber layer (RNFL), and the ganglion cell complex (GCC) were measured by SD-OCT. For ChT values, seven lines at nasal and temporal were drawn at 500-µm intervals, centering the subfoveal sclerochoroidal junction. Analysis of the data was performed with the SPSS program. Mann-Whitney U test was performed for comparison of non-normally distributed continuous data; Student's t test was used for normal distributed data. RESULTS: No significant difference was observed between 70 (66% male; mean age 39.7 ± 10.4 years) axSpA patients (50 radiographic and 20 nr-axSpA) and 50 (mean age 41.2 ± 6.2 years) healthy control subjects (p 0.417). R-axSpA and nr-axSpA groups and control group were similar in terms of spherical equivalent, intraocular pressure, axial length, and body mass index (p 0.574, p 0.874, p 0.918, p 0.344, respectively). While mean macular and GCC thicknesses were significantly lower in the patient group than in the healthy group, there was no significant difference between the two groups in terms of RNFL thickness. CONCLUSION: The present study showed that there was no significant relationship between markers and scores indicating disease activity and ChT, MT, RNFL, and GCC thicknesses. However, an increase in choroidal thickness and involvement of the retinal layers has also been demonstrated in patients with spondyloarthritis. In addition, the relationship between disease activity and retinal layer involvement is remarkable in the r-axSpA group.

Evaluation of serum fibroblast growth factor-23 in patients with axial spondyloarthritis and its association with sclerostin, inflammation, and spinal damage.

The mechanisms underlying new bone formation in individuals with axial spondyloarthritis (axSpA) remain unclear; however, low levels of sclerostin (SOST) may be associated with development of syndesmophytes in those with ankylosing spondylitis (AS). Expression of fibroblast growth factor-23 (FGF-23), another osteocyte factor, is high in those with osteoporosis and chronic renal failure, but levels in those with axSpA are unknown. To evaluate serum FGF-23 and SOST levels in axSpA patients, and to assess their relationship with inflammation and structural damage. In total, 109 axSpA patients (55 with AS and 54 with non-radiographic axSpA) and 57 healthy control (HC) subjects were included in the analysis. Serum concentrations of FGF-23 and SOST were measured and correlation analysis was performed. The presence of syndesmophytes and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) were used to assess structural damage. Levels of serum FGF-23 in axSpA patients were significantly higher than those in HCs [median (interquartile range-IQR) FGF-23 level, pg/ml; AxSpA = 144 (82.3-253.2), HC = 107 (63.3-192.8), p = 0.010]; however, there was no difference in SOST levels. FGF-23 levels correlated with the erythrocyte sedimentation rate (ESR) (r = 0.265, p = 0.006) and serum C-reactive protein (CRP) level (r = 0.229, p = 0.010). In the axSpA, SOST levels correlated negatively with mSASSS (r = - 0.283, p = 0.007), whereas those in the AS group correlated negatively with CRP (r = - 0.426, p = 0.001). Serum FGF-23 levels were high in axSpA patients. Increased FGF-23 was associated with inflammation, but not with SOST levels or disease activity. SOST correlated negatively with both inflammation and structural damage.

Factors Associated with the Development of Anti-drug Antibodies to TNFi and the Consequences for Axial Spondyloarthritis: A Two-year Follow-up Study.

Objective: To evaluate the development of anti-drug antibodies (ADAb) against tumor necrosis factor inhibitors (TNFi) therapy during a 2-year period and search the factors linked to patients with axial spondyloarthritis (axSpA). Methods: Biologic-naive patients with axSpA were included in this observational study. Serum drug levels and ADAb were measured at weeks 12, 24, 52, and 104 of treatment by enzyme-linked immunosorbent assay (ELISA). The development of ADAb and factors related to ADAb over time were investigated using generalized estimating equations (GEE). Results: A total of 180 patients with axSpA (116 male, mean (±SD) 45.6 (±11.9) years) who started TNFi treatment (etanercept (32.2%), adalimumab (27.2%), golimumab (20.6%), infliximab (20%)) were included. In the etanercept treatment group, only 1 patient had ADAb at 12 weeks and 24 weeks. Anti-drug antibodies against TNFi drugs were present in the adalimumab group in 32.7% of patients and in the infliximab group in 21.2% of patients at 12 weeks, and the proportion of ADAb-positive patients were found to be stable throughout the follow-up for adalimumab- and infliximab-treated patients. In the golimumab group, one patient had ADAb against golimumab at 12 weeks and the proportion of ADAb-positive patients increased throughout follow-up. In longitudinal analysis, baseline age, TNFi type, longitudinal Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and ASDAS-CRP scores, serum C-eeactive protein (CRP) levels, presence of adverse events and treatment discontinuation were associated with the presence of ADAb. Conclusion: The development of ADAb against TNFi therapy is associated with younger age, high disease activity, the development of adverse events and more common treatment discontinuation in patients with axSpA during 2-year follow-up.

Non-steroidal anti-inflammatory drug use is determined by disease activity in axSpA and decreased by biologicals: a longitudinal analysis.

OBJECTIVE: To evaluate non-steroidal anti-inflammatory drug (NSAID) use and Assessment in Spondyloarthritis International Society (ASAS)-NSAID scores in patients with axial spondyloarhritis (axSpA) in a longitudinal study. METHODS: In total, 429 patients with axSpA (59% male; 63.6% with AS) were included in this study. Data about disease activity, C-reactive protein (CRP) levels, and NSAID use and dosage were collected at 0, 12, 24, and 52 weeks retrospectively. The relationship with NSAID use /ASAS-NSAID scores and other factors were tested using generalized estimating equations (GEE). RESULTS: At baseline (0 weeks), 92.8% of patients in biologic disease-modifying anti-rheumatic drugs (bDMARDs) group and 82.1% of patients in conventional treatment group were treated with NSAIDs. At baseline, the proportion (p=0.03) and the median (IQR) ASAS-NSAID scores were higher in bDMARDs group [100 (50) vs 50 (83.4); p<0.001]. During follow-up, NSAID use and ASAS-NSAID scores decreased significantly in patients treated with bDMARDs (p<0.001) and the reduction remained stable throughout the follow-up However, neither NSAID use (p=0.06) nor ASAS-NSAID scores changed in conventional treatment group (p=0.15). In bDMARD-treated patients, ASDAS-CRP and BASFI scores were independent determinants for NSAID use, and BASDAI and PGA were determinants for NSAID dosage. There was no independent significant predictor for ASAS-NSAID scores; PGA was the only significant predictor for NSAID use in the conventional treatment group. CONCLUSION: Concurrent biologic treatment was associated with low NSAID intake in patients with axSpA, and NSAID use was determined mainly by disease activity and partly by function during bDMARD treatment.

Does Nasal Secretion Decrease in Sjögren Syndrome and Does This Affect Nasal Function?

OBJECTIVE: Sjögren syndrome is a systemic inflammatory disease causing gland dysfunction. Few (and contradictory) reports on the mucosal effects of Sjögren syndrome have appeared. Here, we objectively demonstrate nasal dryness in Sjögren syndrome patients and explore the effect of such dryness on olfaction. METHODS: Thirty-four consecutive patients with primary Sjögren syndrome were enrolled in this cross-sectional study. The control group consisted of 21 age- and sex-matched volunteers. Medical histories and nasal findings were recorded. The Connecticut Chemosensory Clinical Research Center test was used to evaluate olfactory function. All subjects underwent mucucociliary clearance analysis (the saccharin test and peak nasal inspiratory flowmetry). The intranasal Schirmer test was used to evaluate the nasal cavity. RESULTS: The nasal Schirmer test scores were 8.4 mm (right) and 8 mm (left) (P = .041, P = .016, respectively, compared to controls). The Chi-squared test revealed significant differences (compared to controls) in nasal dryness (P = .001), postnasal drip (P = .04), and smell (a decrease) (P = .005). Neither olfactory function nor mucociliary clearance differed between the groups. We noted a trend toward a positive correlation between olfactory function and the nasal Schirmer score but statistical significance was not attained. CONCLUSION: The intranasal Schirmer test objectively showed that Sjögren syndrome patients exhibited nasal cavity dryness; this is useful in terms of follow-up. This did not affect olfactory function. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:370-373, 2021.

Is the international physical activity questionnaire (IPAQ) a valid assessment tool for measuring physical activity of patients with axial spondyloartritis?

BACKGROUND: Determining the level of physical activity (PA) is an essential part of patient evaluation in axial spondylarthritis (axSpA). Subjective and objective methods are both frequently used methods for evaluating PA. Although subjective methods are cost-effective and easy to use, their accuracy for measuring PA is still questionable. OBJECTIVE: To investigate the concurrent criterion validity of a self-reported questionnaire (IPAQ-Short Form) when compared to an accelerometer (Actigraph wGT3X-BT) for measuring PA level in patients with axSpA. DESIGN: Cross-sectional design. METHODS: Fifty-eight patients with axSpA with a median age of 39.0 (IQR 25/75: 30.0/46.0) years were included in the study. An accelerometer (Actigraph wGT3X-BT) was attached to the waist of patients at their first visits and was removed at their second visits, seven days later. Patients were asked to complete the International Physical Activity Questionnaire Short Form (IPAQ) at their second visits. RESULTS: No significant correlations were determined between IPAQ and accelerometer (p > 0.05), except for the moderate PA (rho: 0.367, p < 0.05), and total PA (rho: 0.330, p < 0.05). It was also observed that IPAQ was underestimating energy expenditure for all types of PA. CONCLUSION: IPAQ might not be a valid tool for measuring PA level in patients with axSpA. Disease-specific subjective methods for determining the PA should be developed and validated for those patients.

Evaluation of subclinical myocardial dysfunction using speckle tracking echocardiography in patients with radiographic and non-radiographic axial spondyloarthritis.

OBJECTIVE: To evaluate whether there is any difference between radiographic axial spondyloarthritis (r-axSpA), also termed ankylosing spondylitis (AS), and non-radiographic (nr-) axSpA, with respect to subclinial myocardial dysfunction using speckle tracking echocardiography (STE). METHODS: This was a cross-sectional case control study. We included 72 patients with AS, 38 patients with nr-axSpA, and 56 age-matched healthy subjects. Patients with cardiac disease and cardiac risk factors affecting STE were excluded. The disease burden evaluated by the BASDAI, BASFI, BAS-G, and ASAS-HI scores were comparable in both the r- and nr-axSpA groups. A detailed echocardiographic examination including the M-mode, Doppler, and STE was applied to whole study population. RESULTS: Duration of the disease, the use of an anti-TNFα agent, and CRP levels were higher in patients with AS. Although the AS, nr-axSpA, and control groups had similar ejection fraction values (59±5.2, 60±4.6, 60±4.6, respectively, and p=0.499), the global longitudinal peak systolic strain (GLS) (20.5±3.3, 21.1±3.5, and 22.3±2.4, respectively, and p<0.05) was different between the groups. In a post-hoc analysis, GLS was not different between the nr-axSpA and control groups, and it was significantly lower in patients with AS. In the univariate analysis, peripheral arthritis (p=0.035) and age (p=0.032) were correlated with GLS. A multivariate regression analysis demonstrated that peripheral arthritis (p=0.009) was the only independent GLS predictor. CONCLUSION: Subclinical myocardial dysfunction as assessed by GLS was present in AS, but not in nr-ax-SpA patients. Thus, GLS could be used as a differentiating factor between radiographic and nr-axSpA patients.

High expression of mesothelin in advanced serous ovarian cancer is associated with poor prognosis.

PURPOSE: Mesothelin is a cell surface glycoprotein which is highly expressed in various types of epithelial cancers. Its expression level is associated with poor prognosis in many cancer types. The aim this study was to evaluate the association of the level of mesothelin expression with clinicopathological characteristics and its prognostic significance in patients with advanced serous ovarian cancer (SOC). METHODS: Tissue blocks from a total 42 patients with advanced SOC treated at the medical oncology clinic of Izmir Katip Celebi University Ataturk Training and Research Hospital between 2006 and 2013 were evaluated. Immunohistochemical staining for mesothelin was performed. Clinical characteristics, optimal or suboptimal operation, response to platinum-based chemotherapy, and overall survival (OS) were analyzed. RESULTS: The cut-off value of 45 for mesothelin H-score determined by ROC analysis predicted survival with 86% sensitivity and 75% specificity (p=0.020). We found a notable negative correlation between mesothelin H-score and OS (r = -0.570, p=0.0001). The median OS was 67 months (95%CI, 36.114 to 97.886) in the low-staining mesothelin H-score group and 27 months (95%CI, 22.238 to 31.762) in the high-staining mesothelin H-score group (p=0.002). Univariate analysis showed that the clinical stage IV disease (p=0.023), platinum chemoresistance (p=0.001), higher mesothelin H-score (p=0.002), and suboptimal surgery (p=0.024) were associated with worse OS. In the multivariate Cox regression model, mesothelin H-score (B=1.15, 95%CI=1.016 to 9.850, p=0.047) and the status of platinum sensitivity (B=-.916, 95%CI=.185 to -.864, p=0.020 were statistically significant predictors for OS. CONCLUSION: These results indicated that high mesothelin H-scores were significantly associated with poor prognosis in patients with advanced SOC.