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49 (816.53, 1073.65) ng/mL vs 824.51 (701.34, 987.06) ng/mL, p=0.014). Serum cfDNA levels were significantly negatively associated with the 1.5-year eGFR change (r=-0.219 p=0.009) and 3-year eGFR change (r=-0.181, p=0.043). Multivariate logistic analyses showed that after adjustment of age, gender, body mass index, fast plasma glucose, smoking, triglycerides, total cholesterol, duration of diabetes, systolic blood pressure, diabetic retinopathy, eGFR, high sensitivity C-reactive protein, angiotensin receptor blocker/ACE inhibitor usage, with the increase of one SD of serum cfDNA levels, the risk of DKD progression increased by 2.4 times (OR, 2.46; 95% CI 1.84 to 4.89). CONCLUSION Serum cfDNA is closely associated with DKD, and it might be a predictor of DKD progression in patients with type 2 diabetes. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.OBJECTIVE Obesity is associated with metabolic abnormalities, including insulin resistance and dyslipidemias. Previous studies demonstrated that genistein intake modifies the gut microbiota in mice by selectively increasing Akkermansia muciniphila, leading to reduction of metabolic endotoxemia and insulin sensitivity. However, it is not known whether the consumption of genistein in humans with obesity could modify the gut microbiota reducing the metabolic endotoxemia and insulin sensitivity. RESEARCH DESIGN AND METHODS 45 participants with a Homeostatic Model Assessment (HOMA) index greater than 2.5 and body mass indices of ≥30 and≤40 kg/m2 were studied. Patients were randomly distributed to consume (1) placebo treatment or (2) genistein capsules (50 mg/day) for 2 months. Blood samples were taken to evaluate glucose concentration, lipid profile and serum insulin. Insulin resistance was determined by means of the HOMA for insulin resistance (HOMA-IR) index and by an oral glucose tolerance test. After 2 months, to control the abnormalities associated with obesity, particularly insulin resistance; however, long-term studies are needed. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND/AIMS To quantify retinal cavitation size over time in macular telangiectasia type 2 (MacTel) and to correlate changes with visual acuity and area of ellipsoid zone loss. METHODS Optical coherence tomography (OCT) macula volume scans from sham eyes included in a prospective, phase II clinical trial of human ciliary neutrophic factor for MacTel at baseline, 1 year and 2 years of follow-up were analysed. Cavitations were segmented by two independent readers. Total cavitation volume was compared with area of ellipsoid zone loss and best-corrected visual acuity (BCVA). RESULTS Fifty-one eyes from 51 unique patients (mean age 62 years, range 45-79 years) were included. Intraclass correlation between readers for cavitation volume was excellent (>0.99). Average cavitation volume was 0.0109 mm3, 0.0113 mm3 and 0.0124 mm3 at baseline, 1 year and 2 years, respectively. The average rate of cavitation volume change was +0.0039 mm3/year. 10 eyes (20%) had a significant change in cavitation volume during the study (3 decreased, 7 increased). Eyes with increased cavitation volume had worse BCVA compared with eyes with no change/decreased cavitation volume (71.5 vs 76.1 ETDRS letters, respectively). Cavitation volume was negatively correlated to BCVA (r=-0.37) but not to area of ellipsoid zone loss. Cavitation volume was negatively predictive of BCVA in both univariate and multivariate mixed-effects modelling with ellipsoid zone loss. CONCLUSIONS Retinal cavitations and their rate of change in MacTel can be reliably quantified using OCT. Cavitations are negatively correlated with visual acuity and may be a useful OCT-based biomarker for disease progression and visual function in MacTel. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.PURPOSE The endothelial and cell-specific angiopoietin-Tie pathway plays an important regulatory role in angiogenesis. In this study, we investigated the associations of the TIE2 (tyrosine kinase, endothelial, TEK) gene with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), using haplotype-tagging single-nucleotide polymorphisms (SNPs) analysis. METHODS This study involved totally 2343 subjects, including a Hong Kong Chinese cohort (214 nAMD patients, 236 PCV patients and 433 control subjects), a Shantou Chinese cohort (189 nAMD patients, 187 PCV patients and 531 control subjects) and an Osaka Japanese cohort (192 nAMD patients, 204 PCV patients and 157 control subjects). Thirty haplotype-tagging SNPs in TIE2 were genotyped in the Hong Kong cohort using TaqMan technology. Two SNPs (rs625767 and rs2273717) showing association in the Hong Kong cohort were genotyped in the Shantou and Osaka cohorts. The SNP-disease association of individual and pooled cohorts were analysed. RESULTS Two SNPs (rs625767 and rs2273717) showed suggestive association with both nAMD and PCV in the Hong Kong cohort. In the meta-analysis involving all the three cohorts, rs625767 showed significant associations with nAMD (p=0.01; OR=0.82, 95% CI 0.70 to 0.96; I2=0%), PCV (p=0.02; OR=0.83, 95% CI 0.71 to 0.97; I2=27%) and pooled nAMD and PCV (p=0.002; OR=0.82, 95% CI 0.72 to 0.93; I2=0%), with low inter-cohort heterogeneities. CONCLUSION This study revealed TIE2 as a novel susceptibility gene for nAMD and PCV in Japanese and Chinese. Further studies in other populations are warranted to confirm its role. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.PURPOSE Severe dry eye is widely prevalent yet difficult to treat. This study aims to evaluate for improvement in epithelial status and the risk factors for lack of improvement in a cohort of patients in Singapore with severe dry eye. see more METHODS We retrospectively identified 1712 patients with severe dry eye (≥grade 3 Delphi) in at least one eye, referred to a tertiary centre dry eye clinic from 2006 to 2017. We included patients with central corneal staining grade of ≥2 at referral and minimum follow-up duration of 6 months (n=407). An epithelial staining grade of less then 2 at the last visit was considered a significantly improved outcome. RESULTS The mean follow-up duration was 4.0±2.4 years, with 88.0% (358/407) of patients achieving significant improvement. Various treatment modalities including topical corticosteroids (32.4%), cyclosporine (52.8%) and punctal plugs (24.1%) were used. Risk factors for non-improvement of staining grade include autoimmune disease (OR 3.2, 95% CI 1.7 to 6.1), rheumatoid arthritis (RA) (OR 3.