IMPORTANCETo our knowledge, a set of well-defined diagnostic criteria is not yet developed for the diagnosis of Vogt-Koyanagi-Harada (VKH) disease.OBJECTIVE To develop and evaluate a set of diagnostic criteria for VKH disease using data from Chinese patients. DESIGN, SETTING, AND PARTICIPANTS This case-control study reviewed medical records of patients from a tertiary referral center between October 2011 and October 2016. Data from 634 patients with VKH disease and 623 patients with non-VKH uveitis from southern China were used to develop the Diagnostic Criteria for VKH Disease (DCV). Data from an additional group of 537 patients with a definite VKH disease diagnosis and 525 patients with non-VKH uveitis from northern China were used to evaluate the diagnostic criteria. MAIN OUTCOMES AND MEASURES Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic. RESULTSOf the 1257 patients used to construct the DCV, 665 (52.9%) were male, and the mean (SD) age at disease onset was 38.6 (13.6) years. The 3-class model and 21 clinical findings were selected by latent class analysis. Variables with a high positive rate in the early-phase or late-phase VKH group or high specificity constituted essential parameters. Constellations of these essential parameters constructed the DCV. The sensitivity and NPV of the DCV were higher than those of the Revised Diagnostic Criteria for VKH Disease (RDC)

Abstract. Patients with chronic kidney disease (CKD) often exhibit associated endothelial dysfunction and inflammation. Systemic inflammation may contribute to the endothelial dysfunction and accelerated thrombosis observed in CKD patients. In this study, we assessed the relationships among endothelial dysfunction, a disintegrin-like and metalloprotease with thrombospondin type 1 repeats 13 (ADAMTS13) activity and levels of inflammatory cytokines in CKD patients. CKD patients were classified into three groups: The chronic glomerulonephritis group (CGN; n=31), the idiopathic nephritic syndrome group (NS; n=32) and the lupus nephritis group (LN; n=41). We measured the plasma levels of tumor necrosis factor-α (TNF-α), von Willebrand factor (VWF) antigen (VWF:Ag) and ADAMTS13 activity using an ELISA-based method in CKD patients (n=104) and normal controls (n=32). The ratio of the VWF:Ag levels to ADAMTS13 activity was calculated. The VWF:Ag levels were significantly higher and the ADAMTS13 activities were significantly lower in the disease groups compared to the controls (P<0.01). ADAMTS13 activity was lower in the NS group compared to the CGN and LN groups (P<0.05). The TNF-α levels were higher in the CKD group compared to the control group (P<0.01). TNF-α was positively correlated with the VWF:Ag levels (r= 0.242, P= 0.013) and negatively correlated with the glomerular filtration rate (GFR) (r=-0.193, P=0.049). ADAMTS13 activity was negatively correlated with the cholesterol levels in CKD patients (r=-0.2, P= 0.042). TNF-α levels in CKD were positively correlated with the VWF:Ag levels and negatively correlated with GFR, which indicates that inflammation may be a major cause of endothelial dysfunction and an index of renal function. The VWF:Ag levels increased and ADAMTS13 activity decreased in CKD patients, which indicates that CKD leads to a prothrombotic state.

These findings suggest that leptin may be involved in the development of VKH disease possibly by promoting an immune response.

<b><i>Background:</i></b> Cardiovascular disease (CVD) is the leading cause of death in haemodialysis (HD) patients. Vascular calcification (VC) is dramatically accelerated and is strongly associated with CVD events and mortality in HD patients. VC coexists with osteoporosis in many studies. Fibroblast growth factor 21 (FGF21) which is known as an adipocytokine is a new hypoglycemic strategy and is inversely related to bone mineral density. <b><i>Methods:</i></b> To evaluate the contribution of FGF21 to VC in HD patients, we detected circulating FGF21 levels and measured the whole thoracic aorta calcification scores (TACS) and calcification scores of the 3 segments of thoracic aorta, including ascending thoracic aorta (ATACS), aortic arch (AoACS), and descending thoracic aorta (DTACS) of our HD patients in this cross-sectional study. In addition, we pre-incubated human aortic endothelial cells (HAECs) with FGF21 in the presence or absence of parathyroid hormone (PTH) in vitro. <b><i>Results:</i></b> The median serum FGF21 level in HD patients was 11-fold higher than that in healthy controls. Ln(FGF21) was positively correlated with Ln(TACS+1), Ln(ATACS+1), Ln(AoACS+1), and Ln(DTACS+1), respectively, in HD patients. Serum FGF21 was independently associated with TACS and ATACS, AoACS, and DTACS. FGF21 which was combined with age, calcium, and intact PTH demonstrated a high area under the curve of 0.84 with optimal sensitivity (84%) and specificity (71%) for the prediction of VC in HD patients. Our vitro results showed that FGF21 enhanced the calcification effect of PTH on HAECs by increasing calcium deposition and endothelial-to-mesenchymal transition. <b><i>Conclusions:</i></b> Circulating FGF21 was notably higher and was a potential predictor and promoter of VC in HD patients.

Unchecked inflammation can result in severe diseases with high mortality, such as macrophage activation syndrome (MAS). MAS and associated cytokine storms have been observed in COVID-19 patients exhibiting systemic hyper-inflammation. Interleukin-18 (IL-18), a proinflammatory cytokine belonging to the IL-1 family, is elevated in both MAS and COVID-19 patients, and its level is known to correlate with the severity of COVID-19 symptoms. IL-18 binds its specific receptor IL-1 Receptor 5 (IL-1R5, also known as IL-18 Receptor alpha chain), leading to the recruitment of the co-receptor, IL-1 Receptor 7 (IL-1R7, also known as IL-18 Receptor beta chain). This heterotrimeric complex then initiates downstream signaling, resulting in systemic and local inflammation. Here, we developed a novel humanized monoclonal anti-IL-1R7 antibody to specifically block the activity of IL-18 and its inflammatory signaling. We characterized the function of this antibody in human cell lines, in freshly obtained peripheral blood mononuclear cells (PBMCs), and in human whole blood cultures. We found that the anti-IL-1R7 antibody significantly suppressed IL-18-mediated NFκB activation, reduced IL-18-stimulated IFNγ and IL-6 production in human cell lines, and reduced IL-18-induced IFNγ, IL-6 and TNFα production in PBMCs. Moreover, the anti-IL-1R7 antibody significantly inhibited LPS- and Candida albicans -induced IFNγ production in PBMCs, as well as LPS-induced IFNγ production in whole blood cultures. Our data suggest that blocking IL-1R7 could represent a potential therapeutic strategy to specifically modulate IL-18 signaling, and may warrant further investigation into its clinical potential for treating IL-18-mediated diseases, including MAS and COVID-19.

Background The goal was to characterize retinal vasculature by quantitative analysis of arteriole-to-venule (A/V) ratio and vessel density in fundus photos taken with the PanOptic iExaminer System. Methods The PanOptic ophthalmoscope equipped with a smartphone was used to acquire fundus photos centered on the optic nerve head. Two fundus photos of a total of 19 eyes from 10 subjects were imaged. Retinal vessels were analyzed to obtain the A/V ratio. In addition, the vessel tree was extracted using deep learning U-NET, and vessel density was processed by the percentage of pixels within vessels over the entire image. Results All images were successfully processed for the A/V ratio and vessel density. There was no significant difference of averaged A/V ratio between the first (0.77 ± 0.09) and second (0.77 ± 0.10) measurements (P = 0.53). There was no significant difference of averaged vessel density (%) between the first (6.11 ± 1.39) and second (6.12 ± 1.40) measurements (P = 0.85). Conclusions Quantitative analysis of the retinal vasculature was feasible in fundus photos taken using the PanOptic ophthalmoscope. The device appears to provide sufficient image quality for analyzing A/V ratio and vessel density with the benefit of portability, easy data transferring, and low cost of the device, which could be used for pre-clinical screening of systemic, cerebral and ocular diseases.

Introduction Osteoporosis is one of the important bone abnormalities in chronic kidney disease-mineral and bone disorder (CKD-MBD) and still lacks a sensitive biomarker to diagnose. Fibroblast growth factor 21 (FGF21) can stimulate bone loss in patients with diabetes and increase in CKD patients. In this study, we investigated whether FGF21 could serve as a biomarker to predict osteoporosis in a haemodialysis cohort. Methods We recorded demographic information, biochemical data, and serum FGF21 and FGF23 levels and measured the CT attenuation values of 339 haemodialysis patients from two large medical centres. We assessed the correlation of CT attenuation values with serum FGF21 and FGF23 levels and tested whether they were independent factors for osteoporosis. ROC curves were constructed to compare the prognostic value of FGF21 and FGF23 for osteoporosis. Results Based on the CT attenuation value, serum FGF21 levels were higher in our osteoporosis group (median 640.86 pg/ml vs. 245.46 pg/ml, P ˂ 0.01). Meanwhile, FGF21 (r = -0.136, P < 0.05) and FGF23 (r = -0.151, P < 0.05) were both negatively associated with osteoporosis. Moreover, FGF21 (β = -0.067, P < 0.05) was an independent factor for osteoporosis. Furthermore, FGF21 combined with age yielded a marked specificity (90.5 %) and sensitivity (61.8 %) in predicting osteoporosis of haemodialysis patients with less residual renal function. Conclusions FGF21 has a positive relationship with the incidence of osteoporosis in patients on haemodialysis. FGF21 combined with age is a good predictive biomarker for osteoporosis in patients on haemodialysis, especially those with less residual renal function.

5312 Patients with chronic kidney disease (CKD) have increased risks of endothelial dysfunction and thrombosis. Systemic inflammation may contribute to the endothelial dysfunction and accelerated thrombosis observed in CKD patients. von Willebrand factor (VWF), a well-known index of endothelial damage, has been reported to increase both in CKD and inflammatory states. ADAMTS13 is a specific VWF-cleaving protease, and some reports suggested that the ratio of VWF and ADAMTS13 maybe more useful in the diagnosis and treatment evaluation of patients in the prothrombotic state. So we assessed the relationships among endothelial dysfunction, ADAMTS13 activity, and levels of inflammatory cytokines in CKD patients. CKD patients were classified into 3 groups: chronic glomerulonephritis group (CGN, n = 31), idiopathic nephritic syndrome group (NS, n = 32), and lupus nephritis group (LN, n = 41). We measured the plasma levels of TNF-α, VWF antigen (VWF:Ag), and ADAMTS13 activity by using an ELISA-based method in CKD patients (n = 104) and normal controls (n = 32). The ratio of the VWF:Ag level to ADAMTS13 activity was calculated. The VWF:Ag level was significantly higher and the ADAMTS13 activity was significantly lower in all the disease groups than in the controls (P < 0.01). ADAMTS13 activity was lower in the NS group than in the CGN and LN groups (P < 0.05) (Table 1). The TNF-α (pg/mL) level was higher in the CKD group than in the control group (CGN: 3.19 ± 1.01; NS: 3.26 ± 1.18; LN: 3.24 ± 1.24; Control: 2.27 ± 1.23; P < 0.01; P < 0.01). TNF-α was positively correlated with the VWF:Ag level (r = 0.242, P = 0.013) and negatively correlated with the glomerular filtration rate (GFR) (r = −0.193, P = 0.049). ADAMTS13 activity was negatively correlated with the cholesterol level in CKD patients (r = −0.2, P = 0.042). TNF-α level in CKD was positively correlated with the VWF:Ag level and negatively correlated with GFR, which suggests that inflammation might be a major cause of endothelial dysfunction and an index for renal function. The VWF:Ag level increased and ADAMTS13 activity decreased in CKD patients, which indicates that CKD leads to a prothrombotic state. Table 1. The plasma VWF:Ag level, ADAMTS13 activity, and the VWF/ADAMTS13 ratio in the CGN, NS, LN, and control groups N VWF (%) ADAMTS13 (%) VWF/ADAMTS13 CGN 31 198.25 ± 140.20** 61.93 ± 22.47**# 3.83 ± 3.29** NS 32 149.94 ± 74.50** 48.87 ± 18.63** 3.42 ± 1.59** LN 41 234.75 ± 134.91**## 67.81 ± 22.30**## 3.79 ± 2.52** CONTROL 32 99.55 ± 21.37 94.37 ± 23.66 1.12 ± 0.37 vs. CONTROL ** P < 0.01; vs. NS ## p < 0.01, # P < 0.05 Disclosures: No relevant conflicts of interest to declare.